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.