Pharmacokinetics of Fosamprenavir plus Ritonavir in HIV-1-infected Adult Subjects with Hepatic Impairment. Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] Journal article

The effect of hepatic impairment on fosamprenavir/ritonavir pharmacokinetics was investigated. Sixty HIV-1 infected subjects, including 13, 20, and 10 subjects with mild, moderate, and severe hepatic impairment, respectively, and 17 subjects with normal hepatic function were enrolled as the comparator group. Subjects with normal hepatic function received fosamprenavir/ritonavir 700/100mg twice daily; whereas, subjects with hepatic impairment received adjusted doses in anticipation of increased exposures. For subjects with mild hepatic impairment, the studied regimen of fosamprenavir 700mg twice daily + ritonavir 100mg once daily delivered 17% higher plasma amprenavir Cmax, 22% higher AUC(0-tau), similar Ctau, and 114% higher unbound Ctau values. For subjects with moderate hepatic impairment, the studied fosamprenavir 300mg twice daily + ritonavir 100mg once daily regimen delivered 27% lower plasma amprenavir Cmax, 27% lower AUC(0-24), 57% lower Ctau, and 21% higher unbound amprenavir Ctau. For subjects with severe hepatic impairment, the studied fosamprenavir 300mg twice daily + ritonavir 100mg once daily regimen delivered 19% lower plasma amprenavir Cmax, 23% lower AUC(0-24), 38% lower Ctau, and similar unbound amprenavir Ctau. With the reduced ritonavir dosing frequency of 100mg once daily, the plasma ritonavir AUC(0-24) was 39% lower, similar, and 40% higher in subjects with mild, moderate, and severe hepatic impairment, respectively. This study supports the use of reduced fosamprenavir/ritonavir doses or dosing frequencies in patients with hepatic impairment. No significant safety issues were identified, however plasma amprenavir and ritonavir exposures were more variable in subjects with hepatic impairment, and these patients should be closely monitored for safety and virologic response.

Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother]