Pharmacokinetics of lopinavir/ritonavir in HIV/hepatitis C virus-coinfected subjects with hepatic impairment

The effect of hepatic impairment on lopinavir/ritonavir pharmocokinetics was investigated. twenty-four HIV-1-infected subjects received lopinavir 400mg/ritonavir 100 mg twice daily prior to and during the study: 6 each with mild or moderate hepatic impairment (and hepatitis C Virus coinfected) and 12 with normal hepatic function. Mild and moderate hepatic impairment showed similar effects on lopinavir pharmacokinetics. When the 2 hepatic impairment groups were combined, lopinavir C-max and AUC(12) were increased 20% to 30% compared to the controls. Hepatic impairment increased unbound lopinovir AUC(12) by 68% and by 56%. The effect of hepatic impairment on low-dose ritonavir pharmacokinetics was more pronounced in the moderate impairment group (181% and 221% increase in AUC(12) and C-max, respectively) than in the mild impairment group (39% and 61 % increase in AUG(12) and C-max, respectively). While lopinavir/ritonavir dose reduction is not recommended in subjects with mild or moderate hepatic impairment, caution should be exercised in this population.