Strategies for control of zidovudine concentrations in serum

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Published in:	Antimicrobial Agents and Chemotherapy Vol. 39; no. 12; pp. 2792 - 2797
Main Authors:	NOORMOHAMED, S. E, HENRY, W. K, RHAME, F. S, BALFOUR, H. H, FLETCHER, C. V
Format:	Journal Article
Language:	English
Published:	Washington, DC American Society for Microbiology 01-12-1995
Subjects:	Adolescent Adult Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral Agents Antiviral Agents - blood Antiviral Agents - pharmacokinetics Bayes Theorem Biological and medical sciences Clinical Trial HIV Infections HIV Infections - blood human immunodeficiency virus Humans Medical sciences Middle Aged Models, Biological Pharmacology. Drug treatments Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S Zidovudine Zidovudine - blood Zidovudine - pharmacokinetics Human Seropositivity Fitting Retroviridae Posology Virus Analog Bayes forecasting Lentivirinae Antiviral Nucleoside Human immunodeficiency virus Pharmacokinetics Pyrimidine nucleoside
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Abstract	Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue AAC About AAC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy AAC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0066-4804 Online ISSN: 1098-6596 Copyright © 2014 by the American Society for Microbiology. For an alternate route to AAC .asm.org, visit: AAC
AbstractList	There are several clinical scenarios in which knowledge of zidovudine disposition may be important. This study evaluated the clinical utility of pharmacokinetic parameters for zidovudine derived from sparse serum concentration data obtained in an outpatient setting. Twelve human immunodeficiency virus-infected participants had two serum zidovudine concentrations determinations obtained on two different clinic visits, 2 to 38 days apart. Zidovudine concentrations were measured by radioimmunoassay. A one-compartment oral absorption model was used to describe zidovudine disposition. Three different approaches were used to estimate pharmacokinetic parameters: Bayesian estimation with one or two concentrations and least squares with one concentration. The ability of these parameters to predict concentrations measured during the second clinic visit was assessed by calculation of precision and bias and compared with predictions using standard fixed or weight-adjusted parameters. Estimated pharmacokinetic parameters for zidovudine were consistent with literature values; there was no statistically significant difference among the parameters calculated with the three estimation strategies. Absorptive phase concentrations were poorly predicted by all methods (mean percent bias, 157 to 249%; mean percent precision, 389 to 537%). Predictive ability for concentrations obtained in the elimination phase was strikingly improved: mean percent bias, -17 to 70%; mean percent precision, 40 to 95%. Bayesian and least-squares estimated parameters were statistically better than fixed-parameter values for predicting concentrations in the elimination phase. These observations provide a modeling framework to determine pharmacokinetic disposition of zidovudine in an individual, screen for the existence of a drug interaction, and conduct concentration-controlled clinical trials. Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue AAC About AAC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy AAC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0066-4804 Online ISSN: 1098-6596 Copyright © 2014 by the American Society for Microbiology. For an alternate route to AAC .asm.org, visit: AAC There are several clinical scenarios in which knowledge of zidovudine disposition may be important. This study evaluated the clinical utility of pharmacokinetic parameters for zidovudine derived from sparse serum concentration data obtained in an outpatient setting. Twelve human immunodeficiency virus-infected participants had two serum zidovudine concentration determinations obtained on two different clinic visits, 2 to 38 days apart. Zidovudine concentrations were measured by radioimmunoassay. A one-compartment oral absorption model was used to describe zidovudine disposition. Three different approaches were used to estimate pharmacokinetic parameters: Bayesian estimation with one or two concentrations and least squares with one concentration. The ability of these parameters to predict concentrations measured during the second clinic visit was assessed by calculation of precision and bias and compared with predictions using standard fixed or weight-adjusted parameters. Estimated pharmacokinetic parameters for zidovudine were consistent with literature values; there was no statistically significant difference among the parameters calculated with the three estimation strategies. Absorptive phase concentrations were poorly predicted by all methods (mean percent bias, 157 to 249%; mean percent precision, 389 to 537%). Predictive ability for concentrations obtained in the elimination phase was strikingly improved: mean percent bias, -17 to 70%; mean percent precision, 40 to 95%. Bayesian and least-squares estimated parameters were statistically better than fixed-parameter values for predicting concentrations in the elimination phase. These observations provide a modeling framework to determine pharmacokinetic disposition of zidovudine in an individual, screen for the existence of a drug interaction, and conduct concentration-controlled clinical trials.
Author	H H Balfour Jr W K Henry C V Fletcher F S Rhame S E Noormohamed
AuthorAffiliation	Department of Pharmacy Practice, University of Minnesota Health Sciences Center, Minneapolis 55455, USA
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Snippet	Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon... There are several clinical scenarios in which knowledge of zidovudine disposition may be important. This study evaluated the clinical utility of...
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SubjectTerms	Adolescent Adult Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral Agents Antiviral Agents - blood Antiviral Agents - pharmacokinetics Bayes Theorem Biological and medical sciences Clinical Trial HIV Infections HIV Infections - blood human immunodeficiency virus Humans Medical sciences Middle Aged Models, Biological Pharmacology. Drug treatments Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S Zidovudine Zidovudine - blood Zidovudine - pharmacokinetics
Title	Strategies for control of zidovudine concentrations in serum
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