Darunavir/ritonavir and hepatic impairment

This study assessed the steady state pharmacokinetics and safety of darunavir/ritonavir (600 mg/100 mg twice daily) in HIV-negative subjects with mild (n=8) or moderate (n=8) hepatic impairment (Child-Pugh classification A [mild] or B [moderate]) compared with matched, HIV-negative, healthy subjects (n=16). Pharmacokinetic profiles were obtained up to 72 hours post-dose for darunavir and 12 hours post-dose for ritonavir on day 7.

Darunavir pharmacokinetics in subjects with mild and moderate hepatic impairment were comparable to those in matched healthy control subjects. In those with mild hepatic impairment, the least square mean ratios relative to healthy subjects for darunavir AUC, Cmax and Cmin were 0.94 (90% CI 0.75, 1.17), 0.88 (90% CI 0.73, 1.07) and 0.83 (90% CI 0.63, 1.10), respectively. In those with moderate hepatic impairment, these values were 1.20 (90% CI 0.90, 1.60), 1.22 (90% CI 0.95, 1.56) and 1.27 (90% CI 0.87, 1.85), respectively. Ritonavir pharmacokinetics were comparable between healthy subjects and those with mild hepatic impairment, but mean exposure was 50% higher in subjects with moderate hepatic impairment. Darunavir/ritonavir was generally well tolerated, regardless of hepatic impairment.

The results of this study show that the pharmacokinetics of darunavir/ritonavir are not affected by mild or moderate hepatic impairment (although there is a trend to increased exposure in moderate impairment). Therefore, dose adjustments of darunavir/ritonavir are not required in patients with mild or moderate hepatic impairment.

Sekar V et al. Pharmacokinetics of multiple-dose darunavir in combination with low-dose ritonavir in individuals with mild-to-moderate hepatic impairment. Clin Pharmacokinet, 2010, 49 (5): 343-350. http://www.ncbi.nlm.nih.gov/pubmed/20384396