Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
Pharmacokinetics and bioavailability of zidovudine and its glucuronidated metabolite in patients with human immunodeficiency virus infection and hepatic disease (AIDS Clinical Trials Group protocol 062).
Antimicrob Agents Chemother. 1995 Dec;39(12):2732-7. Unique Identifier : AIDSLINE MED/96161289 Moore KH; Raasch RH; Brouwer KL; Opheim K; Cheeseman SH; Eyster E; Lemon SM; van der Horst CM; University of North Carolina, Chapel Hill 27599-7360, USA.
Abstract:
The pharmacokinetics of zidovudine (ZDV) are established in patients with various stages of human immunodeficiency virus (HIV) disease. This study was conducted to determine the pharmacokinetic parameters of ZDV in patients with asymptomatic HIV infection and liver disease. HIV-infected volunteers with normal renal function were stratified according to the severity of liver disease (seven of eight were classified as mild). Each subject received a single intravenous dose of ZDV (120 mg) on the first day, followed by a single oral dose of ZDV (200 mg) on the second day. Blood samples were obtained over a 8-h collection interval, and concentrations of ZDV and its glucuronidated metabolite (GZDV) were determined by high-performance liquid chromatography. The following pharmacokinetic parameters were obtained after oral administration of ZDV to HIV-infected patients with mild hepatic disease; these values were compared with previously reported data in healthy volunteers. The area under the curve (AUC) (1,670 +/- 192 ng.h/ml), maximum concentration of drug in serum (1,751 +/- 180 ng/ml), and half-life (2.04 +/- 0.38 h) of ZDV were increased, while the apparent oral clearance (1.57 +/- 0.31 liter/h/kg of body weight) was decreased; AUC (7,685 +/- 1,222 ng.h/ml) and maximum concentration of drug in serum (5,220 +/- 1,350 ng/ml) of GZDV and the AUC ratio of GZDV to ZDV (2.79 +/- 0.43) after oral administration were decreased. ZDV absolute bioavailability was 0.75 +/- 0.15 in HIV-infected patients with hepatic disease. Although the ZDV apparent oral clearance was not impaired as significantly as in patients with biopsy-proven cirrhosis, our results suggest that ZDV, could accumulate in HIV-infected patients with mild hepatic disease because of impaired formation of GZDV. Patients with mild hepatic disease may require dosage adjustment to avoid accumulation of ZDV after extended therapy.
Keywords: Administration, Oral Adult Antiviral Agents/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS Biological Availability Female Human HIV Infections/COMPLICATIONS/*METABOLISM Injections, Intravenous Liver Diseases/COMPLICATIONS/*METABOLISM Male Middle Age Support, U.S. Gov't, P.H.S. Zidovudine/*ANALOGS & DERIVATIVES/ADMINISTRATION & DOSAGE/ *PHARMACOKINETICS CLINICAL TRIAL JOURNAL ARTICLE MULTICENTER STUDY
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Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
