THE PHARMACOKINETICS OF LAMIVUDINE IN PATIENTS WITH IMPAIRED HEPATIC-FUNCTION

Objective: This study was designed to evaluate the effect of hepatic i mpairment on the pharmacokinetics of lamivudine. Methods: Sixteen pati ents not infected with hepatitis B virus or human immunodeficiency vir us who had hepatic impairment due to liver cirrhosis were assigned to moderately or severely impaired groups by clinical signs/symptoms, C-1 4-aminopyrine metabolic activity and caffeine clearance and compared w ith eight healthy controls. Following a 300-mg dose of lamivudine, blo od and urine samples were taken for drug assay. Results: Lamivudine wa s well tolerated in patients with hepatic impairment. There were no st atistical differences in overall lamivudine exposure (in terms of AUC or C-max) or other major pharmacokinetic parameters i.e. CLR, t(max) a nd t(1/2), between healthy control subjects and patients with moderate or severe hepatic impairment. Conclusions: Hepatic impairment does no t warrant dose modification of lamivudine based on this single-dose ph armacokinetic study.