title: Pharmacokinetics of azidothymidine and its major metabolite glucuronylazidothymidine in hemophiliacs coinfected with human immunodeficiency virus and chronic hepatitis C.
abstract: The increasingly reported cholestatic course of liver disease in hemophiliacs coinfected with human immunodeficiency virus (HIV) and hepatitis C (HCV) has been linked with impaired azidothymidine (AZT) metabolism in this patient group. Therefore, we compared the pharmacokinetics of AZT and its glucuronidated metabolite (glucuronylazidothymidine [GAZT]) in HIV/HCV-coinfected hemophiliacs without cirrhosis to HIV-infected patients without chronic hepatitis. Sixteen HIV/HCV-coinfected hemophiliacs without cirrhosis and six HIV-infected patients with negative hepatitis serology and normal liver transaminases received a single 100-mg oral dose of AZT. Subsequently, plasma concentrations of AZT and GAZT were measured during a 6-hour period by high-pressure liquid chromatography (HPLC). Blood samples were taken before and 30, 60, and 90 minutes and 2, 3, 6, and 8 hours after the intake of AZT. Pharmacokinetic parameters of AZT in HIV-infected patients with concomitant chronic hepatitis did not differ significantly as compared to patients without concomitant liver disease. GAZT half-life and mean residence time of GAZT, however, were significantly longer in HIV/HCV-coinfected hemophiliacs as compared to HIV-positive controls without hepatitis. In HIV-infected patients, underlying chronic hepatitis C does not require AZT dose adaptation. Yet despite normal oral clearance of AZT and GAZT, the increase of half-life and mean residence time of GAZT indicates a prolonged hepatic release of GAZT into the circulation of HIV-infected hemophiliacs with noncirrhotic hepatitis C.
authors: Department of Internal Medicine, University of Bonn, Germany.
authors: J K
authors: JK
authors: Rockstroh
authors: C
authors: C
authors: Reichel
authors: H
authors: H
authors: Hille
authors: J
authors: J
authors: Oldenburg
authors: H H
authors: HH
authors: Brackmann
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D005965:Glucuronates / Q000493:pharmacokinetics; D015658:HIV Infections / Q000150:complications / Q000378:metabolism*; D006467:Hemophilia A / Q000150:complications / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D015215:Zidovudine / Q000493:pharmacokinetics*
chemical_list: D019380:Anti-HIV Agents; D005965:Glucuronates; D015215:Zidovudine