Long-term pharmacokinetics of doxorubicin HCl stealth liposomes in patients after polychemotherapy with vinorelbine, cyclophosphamide and prednisone (CCVP)

The concentration-time profiles of Doxorubicin (DOXO) from day 0 to day 21 after i.v. infusion of 25 or 30 mg/m2 doxorubicin HCI stealth liposomes (Caelyx) were investigated in 9 patients receiving combination polychemotherapy with cyclophosphamide, vinorelbine and prednisone. Peak serum concentrati...

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Bibliographic Details
Published in:	European journal of drug metabolism and pharmacokinetics Vol. 26; no. 3; pp. 179 - 184
Main Authors:	LINKESCH, W, WEGER, M, EDER, I, AUNER, H. W, PERNEGG, C, KRAULE, C, CZEJKA, M. J
Format:	Journal Article
Language:	English
Published:	Genève Médecine et hygiène 01-07-2001
Subjects:	Adult Antibiotics, Antineoplastic - administration & dosage Antibiotics, Antineoplastic - blood Antibiotics, Antineoplastic - pharmacokinetics Antineoplastic agents Antineoplastic Combined Chemotherapy Protocols - pharmacology Area Under Curve Biological and medical sciences Chemotherapy Cisplatin - pharmacology Cyclophosphamide - pharmacology Doxorubicin - administration & dosage Doxorubicin - blood Doxorubicin - pharmacokinetics Drug Carriers Drug Interactions Etoposide - pharmacology Female Half-Life Humans Infusions, Intravenous Karnofsky Performance Status Liposomes Lymphoma, Non-Hodgkin - metabolism Male Medical sciences Middle Aged Pharmacology. Drug treatments Prognosis Antineoplastic agent Human Corticosteroid Drug combination Intravenous administration Liposome Prednisone Doxorubicin Long term Multiple dose Ethylene oxide polymer Alkaloid Cyclophosphamide Oxazaphosphinane derivatives Perfusion Nitrogen mustard Dosage form Coated particle Anthracyclins Drug interaction Conjugated compound Pharmacokinetics Vinorelbine
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Summary:	The concentration-time profiles of Doxorubicin (DOXO) from day 0 to day 21 after i.v. infusion of 25 or 30 mg/m2 doxorubicin HCI stealth liposomes (Caelyx) were investigated in 9 patients receiving combination polychemotherapy with cyclophosphamide, vinorelbine and prednisone. Peak serum concentrations occurred from 0.04 to 4.0 days after infusion (mean tmax = 1.79 +/- 1.55 d) with a mean cmax of 4,595 +/- 2,849 ng/ml. A total amount of 12.84 +/- 2.47 mg liposomal DOXO in the plasma volume (Vp = 2,794 + 537 ml) could be estimated at tmax (= 27 % of the mean dose of 47.6 mg). Stealth liposomes were eliminated slowly from the blood with a mean t 1/2el of 1.9 + 0.5 days (MRT was 4.6 + 2.5 days). AUClast values ranged from 8,070 to 33,446 ng/mld (mean 10,987 +/- 9,339 ng/mld). The low plasma clearance (Cltot = 4,681 +/- 2,835 ml/day) and the small volume of distribution (Vz = 11.7 +/- 6.31) suggested that stealth-liposomes were stable in the blood at least for 14 days. Polychemotherapy with Hyper-CCVP schedule did not alter the stability of stealth liposomes, but peak levels of DOXO seemed to be somewhat lower compared to regression analysis of literature data (cmax versus dosage range from 20 to 60 mg/m2). Due to clast occurring between day 12 to 18, no indices for an accumulation of the drug in the blood could be found, when liposomes were given every four weeks.
ISSN:	0378-7966 2107-0180
DOI:	10.1007/BF03190394