Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
Multidose pharmacokinetics of ritonavir and zidovudine in human immunodeficiency virus-infected patients.
Antimicrob Agents Chemother. 1998 Jul;42(7):1788-93. Unique Identifier : AIDSLINE MED/98325452 Cato A 3rd; Qian J; Hsu A; Levy B; Leonard J; Granneman R; Pharmaceutical Products Division, Abbott Laboratories, Abbott; Park, Illinois 60064, USA. acato@ligand.com
Abstract:
The effect of coadministration of ritonavir and zidovudine (ZDV) on the pharmacokinetics of these drugs was investigated in a three-period, multidose, crossover study. Eighteen asymptomatic, human immunodeficiency virus-positive men were assigned randomly to six different sequences of the following three regimens: ZDV (200 mg every 8 h [q8h] alone for 4 days, ritonavir (300 mg q6h) alone for 4 days, and ZDV with ritonavir for 4 days. Ritonavir pharmacokinetics were unaffected by coadministration with ZDV. However, ZDV exposure was reduced by about 26% (P < 0.05) in the presence of ritonavir. The maximum concentration in (Cmax) of ZDV plasma decreased from 748 +/- 375 (mean +/- standard deviation) to 546 +/- 296, and area under the concentration-time curve from 0 to 24 h (AUC0-24) decreased from 3,052 +/- 1,007 to 2,261 +/- 715 when coadministered with ritonavir. In contrast, the ZDV elimination rate constant was unaffected by ritonavir, suggesting that there was no change in ZDV systemic metabolism. Correspondingly, differences in ZDV-glucuronide Cmax and AUC were not statistically significantly different between regimens (P > 0.31). Also, there were no apparent differences in the formation of 3'-amino-3'-deoxythymidine or in the adverse event profiles between the regimens. The lack of change in ritonavir pharmacokinetics suggests that dosage adjustment of ritonavir is unnecessary when it is administered concurrently with ZDV. The clinical relevance of a 26% reduction in ZDV exposure when ZDV is administered with ritonavir is unknown. In addition to other multidrug regimens, the long-term safety and efficacy of coadministration of ritonavir and ZDV is being investigated.
Keywords: CLINICAL TRIAL JOURNAL ARTICLE RANDOMIZED CONTROLLED TRIAL Acquired Immunodeficiency Syndrome/DRUG THERAPY/*METABOLISM Adult Anti-HIV Agents/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS Cross-Over Studies Cytochrome P-450/ANTAGONISTS & INHIB Drug Interactions Drug Therapy, Combination Human HIV Protease Inhibitors/ADMINISTRATION & DOSAGE/PHARMACOKINETICS Male Middle Age Reverse Transcriptase Inhibitors/ADMINISTRATION & DOSAGE/ PHARMACOKINETICS Ritonavir/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS Zidovudine/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS 981230
M98C6943
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Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
