Comparison of the safety and pharmacokinetics of ST-246® after i.v. infusion or oral administration in mice, rabbits and monkeys
ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (i.v.) formulation may be required for some hospitalized patients who are unable to take oral medication. An i.v. formulation has been evaluated in three spec...
Saved in:
| Published in: | PloS one Vol. 6; no. 8; p. e23237 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Public Library of Science
15-08-2011
Public Library of Science (PLoS) |
| Subjects: | |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Abstract | ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (i.v.) formulation may be required for some hospitalized patients who are unable to take oral medication. An i.v. formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation.
The pharmacokinetics of ST-246 after i.v. infusions in mice, rabbits and nonhuman primates (NHP) were compared to those obtained after oral administration. Ten minute i.v. infusions of ST-246 at doses of 3, 10, 30, and 75 mg/kg in mice produced peak plasma concentrations ranging from 16.9 to 238 µg/mL. Elimination appeared predominately first-order and exposure dose-proportional up to 30 mg/kg. Short i.v. infusions (5 to 15 minutes) in rabbits resulted in rapid distribution followed by slower elimination. Intravenous infusions in NHP were conducted at doses of 1 to 30 mg/kg. The length of single infusions in NHP ranged from 4 to 6 hours. The pharmacokinetics and tolerability for the two highest doses were evaluated when administered as two equivalent 4 hour infusions initiated 12 hours apart. Terminal elimination half-lives in all species for oral and i.v. infusions were similar. Dose-limiting central nervous system effects were identified in all three species and appeared related to high C(max) plasma concentrations. These effects were eliminated using slower i.v. infusions.
Pharmacokinetic profiles after i.v. infusion compared to those observed after oral administration demonstrated the necessity of longer i.v. infusions to (1) mimic the plasma exposure observed after oral administration and (2) avoid C(max) associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and i.v. administration. The administration of ST-246 was well tolerated as a slow i.v. infusion. |
|---|---|
| AbstractList | Background ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (IV) formulation may be required for some hospitalized patients who are unable to take oral medication. An IV formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation. Methodology/Principal Findings The pharmacokinetics of ST-246 after IV infusions in mice, rabbits and nonhuman primates (NHP) were compared to those obtained after oral administration. Ten minute IV infusions of ST-246 at doses of 3, 10, 30, and 75 mg/kg in mice produced peak plasma concentrations ranging from 16.9 to 238 [micro]g/mL. Elimination appeared predominately first-order and exposure dose-proportional up to 30 mg/kg. Short IV infusions (5 to 15 minutes) in rabbits resulted in rapid distribution followed by slower elimination. Intravenous infusions in NHP were conducted at doses of 1 to 30 mg/kg. The length of single infusions in NHP ranged from 4 to 6 hours. The pharmacokinetics and tolerability for the two highest doses were evaluated when administered as two equivalent 4 hour infusions initiated 12 hours apart. Terminal elimination half-lives in all species for oral and IV infusions were similar. Dose-limiting central nervous system effects were identified in all three species and appeared related to high C.sub.max plasma concentrations. These effects were eliminated using slower IV infusions. Conclusions/Significance Pharmacokinetic profiles after IV infusion compared to those observed after oral administration demonstrated the necessity of longer IV infusions to (1) mimic the plasma exposure observed after oral administration and (2) avoid C.sub.max associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and IV administration. The administration of ST-246 was well tolerated as a slow IV infusion. ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (IV) formulation may be required for some hospitalized patients who are unable to take oral medication. An IV formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation. The pharmacokinetics of ST-246 after IV infusions in mice, rabbits and nonhuman primates (NHP) were compared to those obtained after oral administration. Ten minute IV infusions of ST-246 at doses of 3, 10, 30, and 75 mg/kg in mice produced peak plasma concentrations ranging from 16.9 to 238 [micro]g/mL. Elimination appeared predominately first-order and exposure dose-proportional up to 30 mg/kg. Short IV infusions (5 to 15 minutes) in rabbits resulted in rapid distribution followed by slower elimination. Intravenous infusions in NHP were conducted at doses of 1 to 30 mg/kg. The length of single infusions in NHP ranged from 4 to 6 hours. The pharmacokinetics and tolerability for the two highest doses were evaluated when administered as two equivalent 4 hour infusions initiated 12 hours apart. Terminal elimination half-lives in all species for oral and IV infusions were similar. Dose-limiting central nervous system effects were identified in all three species and appeared related to high C.sub.max plasma concentrations. These effects were eliminated using slower IV infusions. Pharmacokinetic profiles after IV infusion compared to those observed after oral administration demonstrated the necessity of longer IV infusions to (1) mimic the plasma exposure observed after oral administration and (2) avoid C.sub.max associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and IV administration. The administration of ST-246 was well tolerated as a slow IV infusion. Background ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (IV) formulation may be required for some hospitalized patients who are unable to take oral medication. An IV formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation. Methodology/Principal Findings The pharmacokinetics of ST-246 after IV infusions in mice, rabbits and nonhuman primates (NHP) were compared to those obtained after oral administration. Ten minute IV infusions of ST-246 at doses of 3, 10, 30, and 75 mg/kg in mice produced peak plasma concentrations ranging from 16.9 to 238 µg/mL. Elimination appeared predominately first-order and exposure dose-proportional up to 30 mg/kg. Short IV infusions (5 to 15 minutes) in rabbits resulted in rapid distribution followed by slower elimination. Intravenous infusions in NHP were conducted at doses of 1 to 30 mg/kg. The length of single infusions in NHP ranged from 4 to 6 hours. The pharmacokinetics and tolerability for the two highest doses were evaluated when administered as two equivalent 4 hour infusions initiated 12 hours apart. Terminal elimination half-lives in all species for oral and IV infusions were similar. Dose-limiting central nervous system effects were identified in all three species and appeared related to high C max plasma concentrations. These effects were eliminated using slower IV infusions. Conclusions/Significance Pharmacokinetic profiles after IV infusion compared to those observed after oral administration demonstrated the necessity of longer IV infusions to (1) mimic the plasma exposure observed after oral administration and (2) avoid C max associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and IV administration. The administration of ST-246 was well tolerated as a slow IV infusion. BackgroundST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (i.v.) formulation may be required for some hospitalized patients who are unable to take oral medication. An i.v. formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation.Methodology/principal findingsThe pharmacokinetics of ST-246 after i.v. infusions in mice, rabbits and nonhuman primates (NHP) were compared to those obtained after oral administration. Ten minute i.v. infusions of ST-246 at doses of 3, 10, 30, and 75 mg/kg in mice produced peak plasma concentrations ranging from 16.9 to 238 µg/mL. Elimination appeared predominately first-order and exposure dose-proportional up to 30 mg/kg. Short i.v. infusions (5 to 15 minutes) in rabbits resulted in rapid distribution followed by slower elimination. Intravenous infusions in NHP were conducted at doses of 1 to 30 mg/kg. The length of single infusions in NHP ranged from 4 to 6 hours. The pharmacokinetics and tolerability for the two highest doses were evaluated when administered as two equivalent 4 hour infusions initiated 12 hours apart. Terminal elimination half-lives in all species for oral and i.v. infusions were similar. Dose-limiting central nervous system effects were identified in all three species and appeared related to high C(max) plasma concentrations. These effects were eliminated using slower i.v. infusions.Conclusions/significancePharmacokinetic profiles after i.v. infusion compared to those observed after oral administration demonstrated the necessity of longer i.v. infusions to (1) mimic the plasma exposure observed after oral administration and (2) avoid C(max) associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and i.v. administration. The administration of ST-246 was well tolerated as a slow i.v. infusion. ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (i.v.) formulation may be required for some hospitalized patients who are unable to take oral medication. An i.v. formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation. The pharmacokinetics of ST-246 after i.v. infusions in mice, rabbits and nonhuman primates (NHP) were compared to those obtained after oral administration. Ten minute i.v. infusions of ST-246 at doses of 3, 10, 30, and 75 mg/kg in mice produced peak plasma concentrations ranging from 16.9 to 238 µg/mL. Elimination appeared predominately first-order and exposure dose-proportional up to 30 mg/kg. Short i.v. infusions (5 to 15 minutes) in rabbits resulted in rapid distribution followed by slower elimination. Intravenous infusions in NHP were conducted at doses of 1 to 30 mg/kg. The length of single infusions in NHP ranged from 4 to 6 hours. The pharmacokinetics and tolerability for the two highest doses were evaluated when administered as two equivalent 4 hour infusions initiated 12 hours apart. Terminal elimination half-lives in all species for oral and i.v. infusions were similar. Dose-limiting central nervous system effects were identified in all three species and appeared related to high C(max) plasma concentrations. These effects were eliminated using slower i.v. infusions. Pharmacokinetic profiles after i.v. infusion compared to those observed after oral administration demonstrated the necessity of longer i.v. infusions to (1) mimic the plasma exposure observed after oral administration and (2) avoid C(max) associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and i.v. administration. The administration of ST-246 was well tolerated as a slow i.v. infusion. Background ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (IV) formulation may be required for some hospitalized patients who are unable to take oral medication. An IV formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation. Methodology/Principal Findings The pharmacokinetics of ST-246 after IV infusions in mice, rabbits and nonhuman primates (NHP) were compared to those obtained after oral administration. Ten minute IV infusions of ST-246 at doses of 3, 10, 30, and 75 mg/kg in mice produced peak plasma concentrations ranging from 16.9 to 238 µg/mL. Elimination appeared predominately first-order and exposure dose-proportional up to 30 mg/kg. Short IV infusions (5 to 15 minutes) in rabbits resulted in rapid distribution followed by slower elimination. Intravenous infusions in NHP were conducted at doses of 1 to 30 mg/kg. The length of single infusions in NHP ranged from 4 to 6 hours. The pharmacokinetics and tolerability for the two highest doses were evaluated when administered as two equivalent 4 hour infusions initiated 12 hours apart. Terminal elimination half-lives in all species for oral and IV infusions were similar. Dose-limiting central nervous system effects were identified in all three species and appeared related to high Cmax plasma concentrations. These effects were eliminated using slower IV infusions. Conclusions/Significance Pharmacokinetic profiles after IV infusion compared to those observed after oral administration demonstrated the necessity of longer IV infusions to (1) mimic the plasma exposure observed after oral administration and (2) avoid Cmax associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and IV administration. The administration of ST-246 was well tolerated as a slow IV infusion. |
| Audience | Academic |
| Author | Kasi, Gopi Jones, Kevin F Weimers, William C Samuel, Peter Tan, Ying Leeds, Janet M Amantana, Adams Honeychurch, Kady M Chen, Yali Kickner, Shirley S Lee, Daniel R Weeks, Morgan Yan, X Steven Jordan, Robert Stone, Melialani A Tyavanagimatt, Shanthakumar R Hruby, Dennis E Zima, Daniela Saville, Bradley M Lauzon, Martin McIntyre, Alan |
| AuthorAffiliation | 1 SIGA Technologies, Corvallis, Oregon, United States of America Duke University, United States of America 3 Charles River Laboratories, Quebec, Canada 2 Charles River Laboratories, Reno, Nevada, United States of America |
| AuthorAffiliation_xml | – name: 2 Charles River Laboratories, Reno, Nevada, United States of America – name: Duke University, United States of America – name: 1 SIGA Technologies, Corvallis, Oregon, United States of America – name: 3 Charles River Laboratories, Quebec, Canada |
| Author_xml | – sequence: 1 givenname: Yali surname: Chen fullname: Chen, Yali organization: SIGA Technologies, Corvallis, Oregon, United States of America – sequence: 2 givenname: Adams surname: Amantana fullname: Amantana, Adams – sequence: 3 givenname: Shanthakumar R surname: Tyavanagimatt fullname: Tyavanagimatt, Shanthakumar R – sequence: 4 givenname: Daniela surname: Zima fullname: Zima, Daniela – sequence: 5 givenname: X Steven surname: Yan fullname: Yan, X Steven – sequence: 6 givenname: Gopi surname: Kasi fullname: Kasi, Gopi – sequence: 7 givenname: Morgan surname: Weeks fullname: Weeks, Morgan – sequence: 8 givenname: Melialani A surname: Stone fullname: Stone, Melialani A – sequence: 9 givenname: William C surname: Weimers fullname: Weimers, William C – sequence: 10 givenname: Peter surname: Samuel fullname: Samuel, Peter – sequence: 11 givenname: Ying surname: Tan fullname: Tan, Ying – sequence: 12 givenname: Kevin F surname: Jones fullname: Jones, Kevin F – sequence: 13 givenname: Daniel R surname: Lee fullname: Lee, Daniel R – sequence: 14 givenname: Shirley S surname: Kickner fullname: Kickner, Shirley S – sequence: 15 givenname: Bradley M surname: Saville fullname: Saville, Bradley M – sequence: 16 givenname: Martin surname: Lauzon fullname: Lauzon, Martin – sequence: 17 givenname: Alan surname: McIntyre fullname: McIntyre, Alan – sequence: 18 givenname: Kady M surname: Honeychurch fullname: Honeychurch, Kady M – sequence: 19 givenname: Robert surname: Jordan fullname: Jordan, Robert – sequence: 20 givenname: Dennis E surname: Hruby fullname: Hruby, Dennis E – sequence: 21 givenname: Janet M surname: Leeds fullname: Leeds, Janet M |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21858040$$D View this record in MEDLINE/PubMed |
| BookMark | eNqNku2K1DAYhYusuB96B6IFQRCcmq-m7R9hGfwYWFhwV_-Gt2k6k9k2GZN0cX56Q16EV2a6M7tMQUHa0nL6vKfpyTlNjow1KkmeY5RhWuB3azs4A122iXKGEKGEFo-SE1xRMuME0aOD5-Pk1Ps1QjktOX-SHBNc5iVi6CT5Obf9Bpz21qS2TcNKpR5aFbYpmCbdrMD1IO2NNipo6Ufk6npGGP_9K4U2KJfq7DZLtWkHr0cLF0_oUmh6bbQPDsIoa5P2Wqq3qYO61sHfmffW3Kitf5o8bqHz6tn-fpZ8_fjhev55dnH5aTE_v5hJXuEwy8uCxaspWSVLXFccSc6orAhvFKnavKCN5E1JES4Iq-uWNjnihHKoyhy38c_Pkpc7301nvdin5wWmqOCclXgkFjuisbAWG6d7cFthQYs7wbqlABdj6JSoc4WrWlJWS8JIVUCOeaUaIApHPYfo9X7_taHuVSOViVl0E9PpG6NXYmlvBcU5x4RHg1d7A2e_D8qHfyx5Ty0hripug41mstdeinNW8LIkDOFIZX-h4tGouC2xP62O-mTgzWQgMkH9CEsYvBeLqy__z15-m7KvD9iVgi6svO2GsSR-CrIdKJ313qn2ITmMxFj_-zTEWH-xr38ce3GY-sPQfd_pHzjhAX8 |
| CitedBy_id | crossref_primary_10_1016_j_colsurfb_2022_113101 crossref_primary_10_1093_cid_ciac622 crossref_primary_10_3390_ijms23148021 crossref_primary_10_1177_0272989X14561681 crossref_primary_10_1002_med_21281 crossref_primary_10_1128_AAC_00959_12 crossref_primary_10_3389_fphar_2022_836356 crossref_primary_10_3390_v15010205 crossref_primary_10_1128_cmr_00092_22 crossref_primary_10_1128_AAC_00904_12 crossref_primary_10_1007_s10517_020_05034_x crossref_primary_10_1016_j_coviro_2012_07_004 |
| Cites_doi | 10.1128/AAC.00021-09 10.1016/j.jcv.2007.07.014 10.1128/AAC.47.10.3275-3280.2003 10.1086/587668 10.3201/eid0703.017311 10.1177/135965350701200802 10.4269/ajtmh.2007.76.768 10.1016/j.ccc.2005.06.004 10.7326/0003-4819-126-4-199702150-00001 10.1128/AAC.01303-07 10.1186/1472-698X-9-S1-S2 10.1016/j.antiviral.2008.03.005 10.3390/v2112409 10.1128/AAC.01689-09 10.1021/jm061484y 10.1128/AAC.00879-06 10.1126/science.316.5830.1418 10.1016/j.virusres.2007.04.014 10.3201/eid0706.010602 10.1021/mp8000099 10.1016/S0166-3542(02)00196-1 10.1358/dot.2010.46.2.1437244 10.1128/AAC.01596-08 10.1177/095632020801900302 10.1128/JVI.79.20.13139-13149.2005 10.4269/ajtmh.2005.73.428 10.1086/378357 10.1179/joc.2000.12.3.258 10.1016/S0166-3542(03)00110-4 10.1097/01.inf.0000095433.88772.7e 10.1016/S0166-3542(02)00197-3 10.1097/00042560-199804010-00008 10.2217/17460913.2.1.17 10.1002/jmv.1084 |
| ContentType | Journal Article |
| Copyright | COPYRIGHT 2011 Public Library of Science 2011 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Chen et al. 2011 |
| Copyright_xml | – notice: COPYRIGHT 2011 Public Library of Science – notice: 2011 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: Chen et al. 2011 |
| DBID | CGR CUY CVF ECM EIF NPM AAYXX CITATION IOV ISR 3V. 7QG 7QL 7QO 7RV 7SN 7SS 7T5 7TG 7TM 7U9 7X2 7X7 7XB 88E 8AO 8C1 8FD 8FE 8FG 8FH 8FI 8FJ 8FK ABJCF ABUWG AFKRA ARAPS ATCPS AZQEC BBNVY BENPR BGLVJ BHPHI C1K CCPQU D1I DWQXO FR3 FYUFA GHDGH GNUQQ H94 HCIFZ K9. KB. KB0 KL. L6V LK8 M0K M0S M1P M7N M7P M7S NAPCQ P5Z P62 P64 PATMY PDBOC PIMPY PQEST PQQKQ PQUKI PRINS PTHSS PYCSY RC3 5PM DOA |
| DOI | 10.1371/journal.pone.0023237 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed CrossRef Gale In Context: Opposing Viewpoints Gale In Context: Science ProQuest Central (Corporate) Animal Behavior Abstracts Bacteriology Abstracts (Microbiology B) Biotechnology Research Abstracts Nursing & Allied Health Database (ProQuest) Ecology Abstracts Entomology Abstracts (Full archive) Immunology Abstracts Meteorological & Geoastrophysical Abstracts Nucleic Acids Abstracts Virology and AIDS Abstracts Agricultural Science Collection ProQuest_Health & Medical Collection ProQuest Central (purchase pre-March 2016) Medical Database (Alumni Edition) ProQuest Pharma Collection Public Health Database (Proquest) Technology Research Database ProQuest SciTech Collection ProQuest Technology Collection ProQuest Natural Science Collection Hospital Premium Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) Materials Science & Engineering Database (Proquest) ProQuest Central (Alumni) ProQuest Central Advanced Technologies & Aerospace Collection ProQuest Agriculture & Environmental Science Database ProQuest Central Essentials Biological Science Collection ProQuest Central Technology Collection Natural Science Collection Environmental Sciences and Pollution Management ProQuest One Community College ProQuest Materials Science Collection ProQuest Central Korea Engineering Research Database Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student AIDS and Cancer Research Abstracts SciTech Premium Collection ProQuest Health & Medical Complete (Alumni) ProQuest Materials Science Database Nursing & Allied Health Database (Alumni Edition) Meteorological & Geoastrophysical Abstracts - Academic ProQuest Engineering Collection Biological Sciences Agriculture Science Database Health & Medical Collection (Alumni Edition) PML(ProQuest Medical Library) Algology Mycology and Protozoology Abstracts (Microbiology C) Biological Science Database ProQuest Engineering Database Nursing & Allied Health Premium ProQuest Advanced Technologies & Aerospace Database ProQuest Advanced Technologies & Aerospace Collection Biotechnology and BioEngineering Abstracts Environmental Science Database Materials Science Collection Publicly Available Content Database ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Academic ProQuest One Academic UKI Edition ProQuest Central China Engineering Collection Environmental Science Collection Genetics Abstracts PubMed Central (Full Participant titles) Directory of Open Access Journals |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) CrossRef Agricultural Science Database Publicly Available Content Database ProQuest Central Student ProQuest Advanced Technologies & Aerospace Collection ProQuest Central Essentials Nucleic Acids Abstracts SciTech Premium Collection ProQuest Central China Environmental Sciences and Pollution Management Health Research Premium Collection Meteorological & Geoastrophysical Abstracts Natural Science Collection Biological Science Collection ProQuest Medical Library (Alumni) Engineering Collection Advanced Technologies & Aerospace Collection Engineering Database Virology and AIDS Abstracts ProQuest Biological Science Collection ProQuest One Academic Eastern Edition Agricultural Science Collection ProQuest Hospital Collection ProQuest Technology Collection Health Research Premium Collection (Alumni) Biological Science Database Ecology Abstracts ProQuest Hospital Collection (Alumni) Biotechnology and BioEngineering Abstracts Environmental Science Collection Entomology Abstracts Nursing & Allied Health Premium ProQuest Health & Medical Complete ProQuest One Academic UKI Edition Environmental Science Database ProQuest Nursing & Allied Health Source (Alumni) Engineering Research Database ProQuest One Academic Meteorological & Geoastrophysical Abstracts - Academic Technology Collection Technology Research Database Materials Science Collection ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) ProQuest One Community College ProQuest Natural Science Collection ProQuest Pharma Collection ProQuest Central Genetics Abstracts ProQuest Engineering Collection Biotechnology Research Abstracts Health and Medicine Complete (Alumni Edition) ProQuest Central Korea Bacteriology Abstracts (Microbiology B) Algology Mycology and Protozoology Abstracts (Microbiology C) Agricultural & Environmental Science Collection AIDS and Cancer Research Abstracts Materials Science Database ProQuest Materials Science Collection ProQuest Public Health ProQuest Nursing & Allied Health Source ProQuest SciTech Collection Advanced Technologies & Aerospace Database ProQuest Medical Library Animal Behavior Abstracts Materials Science & Engineering Collection Immunology Abstracts ProQuest Central (Alumni) |
| DatabaseTitleList | MEDLINE Agricultural Science Database |
| Database_xml | – sequence: 1 dbid: DOA name: Directory of Open Access Journals url: http://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: ECM name: MEDLINE url: https://search.ebscohost.com/login.aspx?direct=true&db=cmedm&site=ehost-live sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Sciences (General) Medicine |
| DocumentTitleAlternate | IV vs. PO ST-246 in Mice, Rabbits and Monkeys |
| EISSN | 1932-6203 |
| Editor | Jhaveri, Ravi |
| Editor_xml | – sequence: 1 givenname: Ravi surname: Jhaveri fullname: Jhaveri, Ravi |
| ExternalDocumentID | 1307664815 oai_doaj_org_article_b5e19bc34bc24297a5169eda2e119b5a 2900145211 A476882401 10_1371_journal_pone_0023237 21858040 |
| Genre | Research Support, U.S. Gov't, Non-P.H.S Comparative Study Journal Article Research Support, N.I.H., Extramural |
| GeographicLocations | Oregon United States--US Nevada |
| GeographicLocations_xml | – name: Nevada – name: United States--US – name: Oregon |
| GrantInformation_xml | – fundername: NIAID NIH HHS grantid: HHSN266200600014C – fundername: NIAID NIH HHS grantid: HHSN272200800041C |
| GroupedDBID | --- 123 29O 2WC 3V. 53G 5VS 7RV 7X2 7X7 7XC 88E 8AO 8C1 8CJ 8FE 8FG 8FH 8FI 8FJ A8Z AAFWJ ABDBF ABIVO ABJCF ABUWG ACGFO ACIHN ACIWK ACPRK ADBBV ADRAZ AEAQA AENEX AFKRA AFRAH AHMBA ALIPV ALMA_UNASSIGNED_HOLDINGS AOIJS APEBS ARAPS ATCPS BAWUL BBNVY BBORY BCNDV BENPR BGLVJ BHPHI BKEYQ BPHCQ BVXVI BWKFM CCPQU CGR CS3 CUY CVF D1I D1J D1K DIK DU5 E3Z EAP EAS EBD ECM EIF EMOBN ESTFP ESX EX3 F5P FPL FYUFA GROUPED_DOAJ GX1 HCIFZ HH5 HMCUK HYE IAO IEA IHR IHW INH INR IOV IPNFZ IPY ISE ISR ITC K6- KB. KQ8 L6V LK5 LK8 M0K M1P M48 M7P M7R M7S M~E NAPCQ NPM O5R O5S OK1 P2P P62 PATMY PDBOC PIMPY PQQKQ PROAC PSQYO PTHSS PV9 PYCSY RIG RNS RPM RZL SV3 TR2 UKHRP WOQ WOW ~02 ~KM AAYXX CITATION AFPKN 7QG 7QL 7QO 7SN 7SS 7T5 7TG 7TM 7U9 7XB 8FD 8FK AZQEC C1K DWQXO FR3 GNUQQ H94 K9. KL. M7N P64 PQEST PQUKI PRINS RC3 5PM AAPBV ABPTK N95 |
| ID | FETCH-LOGICAL-c691t-5874587d849c81b960c643c926de29f573dc6d8301724bbf3d506236a9851f053 |
| IEDL.DBID | RPM |
| ISSN | 1932-6203 |
| IngestDate | Sun May 07 16:28:44 EDT 2023 Tue Oct 22 15:11:34 EDT 2024 Tue Sep 17 21:07:40 EDT 2024 Thu Oct 10 17:45:57 EDT 2024 Tue Nov 19 20:42:19 EST 2024 Tue Nov 12 22:37:00 EST 2024 Thu Aug 01 19:16:18 EDT 2024 Thu Aug 01 19:18:53 EDT 2024 Tue Aug 20 22:08:52 EDT 2024 Fri Nov 22 00:36:32 EST 2024 Sat Nov 02 12:25:15 EDT 2024 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 8 |
| Language | English |
| License | This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. Creative Commons Attribution License |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c691t-5874587d849c81b960c643c926de29f573dc6d8301724bbf3d506236a9851f053 |
| Notes | Conceived and designed the experiments: JML YC KMH RJ AA SRT DEH KFJ BMS. Performed the experiments: DZ XSY GK SSK DL KFJ MW WCW MAS AM ML BMS. Analyzed the data: JML YC AA KFJ SRT. Contributed reagents/materials/analysis tools: GK MW WCW MAS PS YT. Wrote the paper: JML YC KMH RJ AA KFJ. |
| OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3156126/ |
| PMID | 21858040 |
| PQID | 1307664815 |
| PQPubID | 1436336 |
| PageCount | e23237 |
| ParticipantIDs | plos_journals_1307664815 doaj_primary_oai_doaj_org_article_b5e19bc34bc24297a5169eda2e119b5a pubmedcentral_primary_oai_pubmedcentral_nih_gov_3156126 proquest_journals_1307664815 gale_infotracmisc_A476882401 gale_infotracacademiconefile_A476882401 gale_incontextgauss_ISR_A476882401 gale_incontextgauss_IOV_A476882401 gale_healthsolutions_A476882401 crossref_primary_10_1371_journal_pone_0023237 pubmed_primary_21858040 |
| PublicationCentury | 2000 |
| PublicationDate | 2011-08-15 |
| PublicationDateYYYYMMDD | 2011-08-15 |
| PublicationDate_xml | – month: 08 year: 2011 text: 2011-08-15 day: 15 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: San Francisco – name: San Francisco, USA |
| PublicationTitle | PloS one |
| PublicationTitleAlternate | PLoS One |
| PublicationYear | 2011 |
| Publisher | Public Library of Science Public Library of Science (PLoS) |
| Publisher_xml | – name: Public Library of Science – name: Public Library of Science (PLoS) |
| References | RO Baker (ref15) 2003; 57 TC Bolken (ref3) 2010; 46 JP Lalezari (ref19) 1997; 126 SR Rosenthal (ref22) 2001; 7 SD Nafziger (ref1) 2005; 21 (ref37) 2009; 58 ref38 A Nitsche (ref6) 2007; 40 J Neyts (ref16) 2003; 57 A Goff (ref12) 2007; 128 R Jordan (ref33) 2008; 52 S Vora (ref36) 2008; 46 JP Lalezari (ref17) 1998; 17 S Parker (ref4) 2007; 2 DF Smee (ref11) 2008; 19 (3) Review D McCabe (ref14) 2003; 22 R Jordan (ref35) 2010; 54 P Duclos (ref2) 2009; 9 DC Quenelle (ref10) 2003; 47 J Kaiser (ref5) 2007; 316 K Geerinck (ref13) 2001; 64 S Duraffour (ref27) 2007; 12 DC Quenelle (ref28) 2007; 51 G Yang (ref24) 2005; 79 U Eriksson (ref9) 2008; 5 J Cono (ref21) 2003; 52 TR Bailey (ref25) 2007; 50 R Jordan (ref34) 2010; 2 V Papastamopoulos (ref18) 2000; 12 SL Ciesla (ref20) 2003; 59 YJ Hutin (ref8) 2001; 7 R Jordan (ref32) 2009; 53 A Nalca (ref30) 2008; 79 J Huggins (ref31) 2009; 53 Y Chen (ref26) 2009; 6 LA Learned (ref7) 2005; 73 MS Massoudi (ref23) 2003; 188 E Sbrana (ref29) 2007; 76 |
| References_xml | – volume: 53 start-page: 2620 issue: 6 year: 2009 ident: ref31 article-title: Nonhuman primates are protected from smallpox virus or monkeypox virus challenges by the antiviral drug ST-246. publication-title: Antimicrob Agents Chemother doi: 10.1128/AAC.00021-09 contributor: fullname: J Huggins – volume: 40 start-page: 160 issue: 2 year: 2007 ident: ref6 article-title: Viremia in human Cowpox virus infection. publication-title: J Clin Virol doi: 10.1016/j.jcv.2007.07.014 contributor: fullname: A Nitsche – volume: 47 start-page: 3275 issue: 10 year: 2003 ident: ref10 article-title: Efficacy of multiple- or single-dose cidofovir against vaccinia and cowpox virus infections in mice.” publication-title: Antimicrob Agents Chemother doi: 10.1128/AAC.47.10.3275-3280.2003 contributor: fullname: DC Quenelle – volume: 46 start-page: 1555 issue: 10 year: 2008 ident: ref36 article-title: Severe Eczema Vaccinatum in a Household Contact of a Smallpox Vaccinee. publication-title: CID doi: 10.1086/587668 contributor: fullname: S Vora – volume: 7 start-page: 434 issue: 3 year: 2001 ident: ref8 article-title: Outbreak of human monkeypox, Democratic Republic of Congo, 1996 to 1997. publication-title: Emerg Infect Dis doi: 10.3201/eid0703.017311 contributor: fullname: YJ Hutin – volume: 12 start-page: 1205 year: 2007 ident: ref27 article-title: Activity of the anti-orthopoxvirus compound ST-246 against vaccinia, cowpox and camelpox viruses in cell monolayers and organotypic raft cultures. publication-title: Antiviral Therapy doi: 10.1177/135965350701200802 contributor: fullname: S Duraffour – volume: 76 start-page: 768 issue: 4 year: 2007 ident: ref29 article-title: Efficacy of the antipoxvirus compound ST-246 for treatment of severe orthopoxvirus infection.” publication-title: Am J Trop Med Hyg doi: 10.4269/ajtmh.2007.76.768 contributor: fullname: E Sbrana – volume: 58 start-page: 532 issue: 19 year: 2009 ident: ref37 article-title: Progressive Vaccinia in a Military Smallpox Vaccinee — United States, 2009. publication-title: MMWR – volume: 21 start-page: 739 issue: 4 year: 2005 ident: ref1 article-title: Smallpox. publication-title: Crit Care Clin doi: 10.1016/j.ccc.2005.06.004 contributor: fullname: SD Nafziger – volume: 126 start-page: 257 issue: 4 year: 1997 ident: ref19 article-title: Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS. A randomized, controlled trial. publication-title: Ann Intern Med doi: 10.7326/0003-4819-126-4-199702150-00001 contributor: fullname: JP Lalezari – volume: 52 start-page: 1721 issue: 5 year: 2008 ident: ref33 article-title: Single-dose safety and pharmacokinetics of ST-246, a novel orthopoxvirus egress inhibitor. publication-title: Antimicrob Agents Chemother doi: 10.1128/AAC.01303-07 contributor: fullname: R Jordan – volume: 9 start-page: S2 year: 2009 ident: ref2 article-title: Global immunization: status, progress, challenges and future. publication-title: BMC International Health and Human Rights doi: 10.1186/1472-698X-9-S1-S2 contributor: fullname: P Duclos – volume: 79 start-page: 121 issue: 2 year: 2008 ident: ref30 article-title: Evaluation of orally delivered ST-246 as postexposure prophylactic and antiviral therapeutic in an aerosolized rabbitpox rabbit model.” publication-title: Antiviral Res doi: 10.1016/j.antiviral.2008.03.005 contributor: fullname: A Nalca – volume: 2 start-page: 2409 year: 2010 ident: ref34 article-title: Development of ST-246® for Treatment of Poxvirus Infections. publication-title: Viruses doi: 10.3390/v2112409 contributor: fullname: R Jordan – volume: 54 start-page: 2560 issue: 6 year: 2010 ident: ref35 article-title: Safety and pharmacokinetics of the antiorthopoxvirus compound ST-246 following repeat oral dosing in healthy adult subjects. publication-title: Antimicrob Agents Chemother doi: 10.1128/AAC.01689-09 contributor: fullname: R Jordan – volume: 50 start-page: 1442 issue: 7 year: 2007 ident: ref25 article-title: N-(3,3a,4,4a,5,5a,6,6a-Octahydro-1,3-dioxo-4,6- ethenocycloprop[f]isoindol-2-(1H)-yl)carboxamides: Identification of novel orthopoxvirus egress inhibitors. publication-title: J Med Chem doi: 10.1021/jm061484y contributor: fullname: TR Bailey – volume: 51 start-page: 689 issue: 2 year: 2007 ident: ref28 article-title: Efficacy of delayed treatment with ST-246 given orally against systemic orthopoxvirus infections in mice.” publication-title: Antimicrob Agents Chemother doi: 10.1128/AAC.00879-06 contributor: fullname: DC Quenelle – volume: 316 start-page: 1418 issue: 5830 year: 2007 ident: ref5 article-title: A Tame Virus Runs Amok. publication-title: Science doi: 10.1126/science.316.5830.1418 contributor: fullname: J Kaiser – volume: 128 start-page: 88 issue: 1–2 year: 2007 ident: ref12 article-title: In vivo imaging of cidofovir treatment of cowpox virus infection.” publication-title: Virus Res doi: 10.1016/j.virusres.2007.04.014 contributor: fullname: A Goff – volume: 7 start-page: 920 issue: 6 year: 2001 ident: ref22 article-title: Developing New Smallpox Vaccines.” publication-title: Emerging Infectious Diseases doi: 10.3201/eid0706.010602 contributor: fullname: SR Rosenthal – volume: 6 start-page: 1 issue: 44 year: 2009 ident: ref26 article-title: Vaccinia virus p37 interacts with host proteins associated with LE-derived transport vesicle biogenesis.” publication-title: Virol J contributor: fullname: Y Chen – volume: 5 start-page: 598 issue: 4 year: 2008 ident: ref9 article-title: Serine peptide phosphoester prodrugs of cyclic cidofovir: synthesis, transport, and antiviral activity. publication-title: Mol Pharm doi: 10.1021/mp8000099 contributor: fullname: U Eriksson – volume: 57 start-page: 13 issue: 1–2 year: 2003 ident: ref15 article-title: Potential antiviral therapeutics for smallpox, monkeypox and other orthopoxvirus infections.” publication-title: Antiviral Res doi: 10.1016/S0166-3542(02)00196-1 contributor: fullname: RO Baker – volume: 52 start-page: 1 issue: RR04 year: 2003 ident: ref21 article-title: Smallpox Vaccination and Adverse Reactions.” publication-title: MMWR contributor: fullname: J Cono – volume: 46 start-page: 109 issue: 2 year: 2010 ident: ref3 article-title: Tecovirimat for smallpox infections. publication-title: Drugs Today (Barc) doi: 10.1358/dot.2010.46.2.1437244 contributor: fullname: TC Bolken – volume: 53 start-page: 1817 issue: 5 year: 2009 ident: ref32 article-title: ST-246 antiviral efficacy in a nonhuman primate monkeypox model: determination of the minimal effective dose and human dose justification. publication-title: Antimicrob Agents Chemother doi: 10.1128/AAC.01596-08 contributor: fullname: R Jordan – volume: 19 (3) Review start-page: 115 year: 2008 ident: ref11 article-title: Progress in the discovery of compounds inhibiting orthopoxviruses in animal models. publication-title: Antivir Chem Chemother doi: 10.1177/095632020801900302 contributor: fullname: DF Smee – volume: 79 start-page: 13139 issue: 20 year: 2005 ident: ref24 article-title: An orally bioavailable antipoxvirus compound (ST-246) inhibits extracellular virus formation and protects mice from lethal orthopoxvirus Challenge. publication-title: J Virol doi: 10.1128/JVI.79.20.13139-13149.2005 contributor: fullname: G Yang – volume: 73 start-page: 428 issue: 2 year: 2005 ident: ref7 article-title: Extended interhuman transmission of monkeypox in a hospital community in the Republic of the Congo, 2003. publication-title: Am J Trop Med Hyg doi: 10.4269/ajtmh.2005.73.428 contributor: fullname: LA Learned – ident: ref38 – volume: 188 start-page: 973 issue: 7 year: 2003 ident: ref23 article-title: Effectiveness of postexposure vaccination for the prevention of smallpox: results of a delphi analysis.” publication-title: J Infect Dis doi: 10.1086/378357 contributor: fullname: MS Massoudi – volume: 12 start-page: 258 issue: 3 year: 2000 ident: ref18 article-title: Stavrianeas NG. “Lack of reactivation of cytomegalovirus retinitis in an AIDS patient, during and after stopping long-term cidofovir treatment: case report.” publication-title: J Chemother doi: 10.1179/joc.2000.12.3.258 contributor: fullname: V Papastamopoulos – volume: 59 start-page: 163 issue: 3 year: 2003 ident: ref20 article-title: Esterification of cidofovir with alkoxyalkanols increases oral bioavailability and diminishes drug accumulation in kidney.” publication-title: Antiviral Res Aug; doi: 10.1016/S0166-3542(03)00110-4 contributor: fullname: SL Ciesla – volume: 22 start-page: 1027 issue: 11 year: 2003 ident: ref14 article-title: Treatment of orf poxvirus lesion with cidofovir cream.” publication-title: Pediatr Infect Dis J doi: 10.1097/01.inf.0000095433.88772.7e contributor: fullname: D McCabe – volume: 57 start-page: 25 issue: 1–2 year: 2003 ident: ref16 article-title: Therapy and short-term prophylaxis of poxvirus infections: historical background and perspectives.” publication-title: Antiviral Res doi: 10.1016/S0166-3542(02)00197-3 contributor: fullname: J Neyts – volume: 17 start-page: 339 issue: 4 year: 1998 ident: ref17 article-title: Randomized, controlled study of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS.” publication-title: J Acquir Immune Defic Syndr Hum Retrovirol doi: 10.1097/00042560-199804010-00008 contributor: fullname: JP Lalezari – volume: 2 start-page: 17 year: 2007 ident: ref4 article-title: Human monkeypox: an emerging zoonotic disease.” publication-title: Future Microbiol doi: 10.2217/17460913.2.1.17 contributor: fullname: S Parker – volume: 64 start-page: 543 issue: 4 year: 2001 ident: ref13 article-title: A case of human orf in an immunocompromised patient treated successfully with cidofovir cream. publication-title: J Med Virol doi: 10.1002/jmv.1084 contributor: fullname: K Geerinck |
| SSID | ssj0053866 |
| Score | 2.5667217 |
| Snippet | ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (i.v.)... Background ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (IV)... ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (IV) formulation... BackgroundST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (i.v.)... Background ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (IV)... |
| SourceID | plos doaj pubmedcentral proquest gale crossref pubmed |
| SourceType | Open Website Open Access Repository Aggregation Database Index Database |
| StartPage | e23237 |
| SubjectTerms | Administration, Oral Animals Antiviral agents Antiviral Agents - administration & dosage Antiviral Agents - adverse effects Antiviral Agents - pharmacokinetics Area Under Curve Benzamides - administration & dosage Benzamides - adverse effects Benzamides - pharmacokinetics Bioavailability Biological Availability Central nervous system Comparative analysis Disease control Dose-Response Relationship, Drug Drug dosages Drug Evaluation, Preclinical - methods Eczema Exposure FDA approval Female Half-life Health aspects Humans Immunization Infection Infections Infusions, Intravenous Intravenous administration Isoindoles - administration & dosage Isoindoles - adverse effects Isoindoles - pharmacokinetics Laboratories Macaca fascicularis Male Medicine Metabolic Clearance Rate Mice Mice, Inbred BALB C Monkeys Monkeys & apes Oral administration Pharmacokinetics Pharmacology Plasma physics Primates Rabbits Safety regulations Smallpox Species Studies Time Factors Tissue Distribution Toxicity Toxicology Tremor - chemically induced Vaccines Viruses |
| SummonAdditionalLinks | – databaseName: Directory of Open Access Journals dbid: DOA link: http://sdu.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lb9QwELZgT1wQ5dWFAhZCAiSyjZPYjo-ltCoXkNiCuEV-wgqUrDa7SBz5Q_wIfhkziRM1qBIcuMazq2Qe9je25xtCngTBg8tFkYjU8wScIk-MyUJirJRWe654ioXCZ0v55mP56gRpcsZWX3gnrKcH7hV3aLhnyti8MBZWEyU1Hux4pzPP4DnvoVEqhmSqn4MhioWIhXK5ZIfRLot1U3vcQskz7Ht-YSHq-PrHWXm2_tq0l0HOP29OXliKTm-Q6xFD0qP-3ffIFV_fJHsxSlv6LFJJP79FfhyPbQZpEyiAPdrq4Lffqa4dXUfa6i-ANJGtGUWW50lWiF8_adc8nK4W3xYUnHCHm2q02VAs6Kd6wrgL4xSb2r-gG23Matt2fw7uDfNDe5u8Pz05Pz5LYtOFxArFtglH_vtSurJQFiAtJDgWQItVmXA-U4HL3Fnhyhxzx8KYkDueAoQSWgF2C6D5O2RWg5r3Cc2kLL1XqcUsRwRYCJ1QwZVMaBaY1XOSDBao1j23RtUdsEnISXpVVmixKlpsTl6imUZZZMbuHoC_VNFfqr_5y5w8QiNXfZnpGN_VUQGJVwn4hs3J404C2TFqvH7zSe_atnr99sM_CC3fTYSeRqHQgEmsjiUP8E3IujWRPJhIQozbyfA-uuSglRYPIaUQSLQDvxzc9PLhu73HjloDTMdLmLrnRE58eaLW6Ui9-twRj-cMe6mKe__DDvfJtWF7nvEDMttudv4Budq63cMulH8DWGBN2Q priority: 102 providerName: Directory of Open Access Journals |
| Title | Comparison of the safety and pharmacokinetics of ST-246® after i.v. infusion or oral administration in mice, rabbits and monkeys |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/21858040 https://www.proquest.com/docview/1307664815 https://pubmed.ncbi.nlm.nih.gov/PMC3156126 https://doaj.org/article/b5e19bc34bc24297a5169eda2e119b5a http://dx.doi.org/10.1371/journal.pone.0023237 |
| Volume | 6 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://sdu.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9NAEF6RHBAXRMujgVJWCAmQcBI_dtc-ltCqOYRWTam4Wet9lIjWjuLkwIl_xI_glzGzXkc16gFx9Y5f89qZ3ZlvCXljObM65knAx4YFoBRxUBSRDQolhJKGZWyMjcInc_H5a_rpCGFyWNsL44r2VbEYltc3w3LxzdVWLm_UqK0TG53NJnGIZzryUY_0IDZsU_TG_YIBc-575GIRjrxIhsuqNLh6EkexcAjAKUvHuORxazpyqP1b39xfXlf1XYHn3_WTtyak40fkoY8k6WHzxTvknil3yf2Z3yvfJTvebGv6zmNLv39Mfk625w7SylKI_uhcWrP-QWWp6ZnHsf4OD0D4ZiSZXwRRwn__ou40cTq9pNPSbnCNjVYrerrCT-gA8NJFSWfgfj7Qc1kUi3XtHg2-A9xF_YR8OT66mJwE_gyGQPEsXAcM4fBTodMkUxDhQr6jIIZRWcS1iTLLRKwV12mMqWRSFDbWbAwRFZcZhHIWpPGU9Etg_R6hkRCpMdlYYdLDLcyLmmdWpyGXoQ2VHJCgFUW-bKA2crffJiBFaXiaoxRzL8UB-Yjy2tIiULa7UK2ucq8uecFMmBUqTgoFwUgmJO4LGi0jE8J1Bi99hdLOm67TrbnnhwnkYSmEO-GAvHYUCJZRYjXOldzUdT49vfwHovl5h-itJ7IViERJ3wEB_4QgXB3K_Q4lmLzqDO-hbrZcqXFPUnCOuDtwZ6uvdw8_a1R3y7XWEAZEdJS6w9buCJilwyH3Zvj8v-98QR60S_Qh2yf99WpjXpJerTcHbm3kwFn2H_cFUGs |
| link.rule.ids | 230,315,729,782,786,866,887,2106,27933,27934,53800,53802 |
| linkProvider | National Library of Medicine |
| linkToHtml | http://sdu.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LbxMxELZokIBLoeXRQKEWQgIkNtmX7d1jCa0S0bRVEypuq7XXLlHb3SibHDjxj_gR_DJmdr1RF_WAerVnH_Y8PGPPfCbkneHMZAEPHe5q5oBQBI6UvnGkEkKlmsXMxULh4UQcf4--HCBMDmtqYaqkfSVnvfzqupfPflS5lfNr1W_yxPqn40Hg4Z2OvL9B7oO-um4TpNcGGJo4t1VygfD6lim9eZFr3D8J_EBUGMARi1zc9LixIFW4_Wvr3JlfFeVtrue_GZQ3lqTDx3cczBOyaX1Qul93b5F7Ot8mD8b2lH2bbFmFL-kHi0r98Sn5NVjfWEgLQ8FvpJPU6OVPmuYZPbUI2JfwAgR-RpLJ1PFD_uc3re4hp6NzOsrNCnfnaLGgJwv8hRZ0L53ldAyG6xM9S6WcLcvq1WB1wNCUz8i3w4PpYOjY2xscxWNv6TAE0o9EFoWxAt8YIiUF3o-KfZ5pPzZMBJniWRRgEBpKaYKMueCL8TQGJ9AAF5-TTg4s2yHUFyLSOnYVhkvcwIqa8dhkkcdTz3gq7RKnYWEyr0E6kuqkTkBwU89pgtxPLPe75DPyeU2LENtVQ7G4SCxvEsm0F0sVhFKBGxOLFE8UdZb62oN2Bh_dQylJ6nrVtaFI9kOI4CJwlLwueVtRIMxGjnk8F-mqLJPRyfl_EE3OWkTvLZEpgCUqtbUTMCaE72pR7rYowVioVvcOynQzKyWeZgrOEbEHnmzk_PbuF7XIr2etUaAuES1laE1ruwd0oEIwtzL_8s5P7pGHw-n4KDkaHX99RR41G_0e2yWd5WKlX5ONMlu9qezCXzsbZPY |
| linkToPdf | http://sdu.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1Lb9QwELboIlVcgJZHFwq1EBIgkd087eRYtq26gm1X3VJxi-JXWdEmq83ugRP_iB_BL2MmcaIG9YDgak8e9jw8Y4-_IeS1YZFRAQsd5urIAaEIHCF84wjJucx0lEQuXhQ-nvGTL_HBIcLktKW-qqR9KeaD_Op6kM-_VrmVi2s5bPLEhtPJKPCwpiMbLpQZbpC7oLOu3wTqtRGGJsbsTbmAe0PLmMGiyDXuoQR-wCsc4DiKXdz4uLEoVdj9rYXuLa6K8jb3888syhvL0tGD_xjQQ3Lf-qJ0vybZInd0vk02J_a0fZtsWcUv6VuLTv3uEfkxaisX0sJQ8B_pLDN69Z1muaJTi4T9DV6AANBIMjt3_JD9-kmreuR0fEHHuVnjLh0tlvR0ib_QgfCl85xOwIC9p2eZEPNVWb0arA8YnPIx-Xx0eD46dmwVB0eyxFs5EQLqx1zFYSLBR4aISYIXJBOfKe0nJuKBkkzFAQajoRAmUJELPhnLEnAGDXDyCenlwLYdQn3OY60TV2LYxAysrIolRsUeyzzjyaxPnIaN6aIG60irEzsOQU49pylKQGoloE8-IK9bWoTarhqK5WVq-ZOKSHuJkEEoJLgzCc_wZFGrzNcetEfw0T2UlLS-t9oajHQ_hEguBofJ65NXFQXCbeSYz3OZrcsyHZ9e_AXR7KxD9MYSmQJYIjN7hwLGhDBeHcrdDiUYDdnp3kG5bmalxFNNzhgi98CTjazf3v20Fvt21hol6hPeUYjOtHZ7QA8qJHMr98_--ck9sjk9OEo_jU8-Pif3mv1-L9olvdVyrV-QjVKtX1am4TdjO2d2 |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Comparison+of+the+Safety+and+Pharmacokinetics+of+ST-246%C2%AE+after+IV+Infusion+or+Oral+Administration+in+Mice%2C+Rabbits+and+Monkeys&rft.jtitle=PloS+one&rft.au=Chen%2C+Yali&rft.au=Adams+Amantana&rft.au=Tyavanagimatt%2C+Shanthakumar+R&rft.au=Zima%2C+Daniela&rft.date=2011-08-15&rft.pub=Public+Library+of+Science&rft.eissn=1932-6203&rft.volume=6&rft.issue=8&rft.spage=e23237&rft_id=info:doi/10.1371%2Fjournal.pone.0023237&rft.externalDBID=HAS_PDF_LINK&rft.externalDocID=2900145211 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1932-6203&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1932-6203&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1932-6203&client=summon |