Factor V:Q506 mutation-resistance to activated protein C (APC): clinical implications with respect to family screening

OBJECTIVE: This study was designed to evaluate the effect of hepatic impairment on the pharmacokinetics of lamivudine. METHODS: Sixteen patients not infected with hepatitis B virus or human immunodeficiency virus who had hepatic impairment due to liver cirrhosis were assigned to moderately or severely impaired groups by clinical signs/symptoms, 14C-aminopyrine metabolic activity and caffeine clearance and compared with eight healthy controls. Following a 300-mg dose of lamivudine, blood and urine samples were taken for drug assay. RESULTS: Lamivudine was well tolerated in patients with hepatic impairment. There were no statistical differences in overall lamivudine exposure (in terms of AUC or Cmax) or other major pharmacokinetic parameters i.e. CLR, tmax and t1/2, between healthy control subjects and patients with moderate or severe hepatic impairment. CONCLUSIONS: Hepatic impairment does not warrant dose modification of lamivudine based on this single-dose pharmacokinetic study.