Pharmacokinetics of azidothymidine and its major metabolite glucuronylazidothymidine in hemophiliacs coinfected with human immunodeficiency virus and chronic hepatitis C.

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.