Lopinavir/ritonavir pharmacokinetics in HIV and hepatitis C virus co-infected patients without liver function impairment: influence of liver fibrosis

Clin Pharmacokinet. 2007;46(1):85-92. doi: 10.2165/00003088-200746010-00005.


Background and objective: To assess the influence of hepatitis C virus (HCV) co-infection and the extent of liver fibrosis on lopinavir/ritonavir pharmacokinetics in HIV-infected patients without liver function impairment.

Methods: Cross-sectional, comparative study enrolling HIV-infected adults receiving lopinavir/ritonavir (400 mg/100 mg twice daily). HIV/HCV co-infected patients were grouped as having advanced fibrosis (HCV+/FIB+, n=7) or not (HCV+/FIB-, n=8) based on the FIB-4 index. A full concentration-time profile was obtained for each patient, and blood samples were collected before (0), and 1, 2, 4, 6, 8, 10 and 12 hours after a lopinavir/ritonavir dose. Lopinavir and ritonavir concentrations in plasma were determined by high-performance liquid chromatography. Maximum and minimum plasma concentrations (Cmax and Cmin), area under the plasma concentration-time curve from 0 to 12 hours (AUC12), apparent oral clearance at steady state (CLss/F), and apparent volume of distribution after oral administration (Vd/F) were calculated for each individual using a non-compartmental approach.

Results: Twenty-six HCV- and 22 HCV+patients were enrolled. Lopinavir and ritonavir pharmacokinetics were comparable between HCV- and HCV+patients. However, the Vd/F of lopinavir was 125% higher in HCV+/FIB+patients than in HCV-patients (p=0.015) and 107% higher than in HCV+/FIB-(p=0.040) patients. The CLss/F of ritonavir was 40% lower in HCV+/FIB+patients than in HCV-patients (p=0.005) and 44% lower than in HCV+/FIB-patients (p=0.040). Thus, for ritonavir AUC12, Cmax and Cmin in HCV+/FIB+patients were 63%, 86% and 100% higher, respectively, when compared with those parameters in HCV-patients (p=0.005, p=0.012 and p=0.015, respectively), and 80%, 86% and 100% higher, respectively, when compared with levels in HCV+/FIB- patients (p=0.040, p=0.040 and p=0.029, respectively).

Conclusion: Lopinavir exposure is similar in HIV-infected patients with or without HCV co-infection and without liver function impairment. However, ritonavir exposure may be higher in this setting, particularly in individuals with advanced liver fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Area Under Curve
  • Chromatography, High Pressure Liquid
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / physiopathology
  • HIV Protease Inhibitors / pharmacokinetics*
  • HIV Protease Inhibitors / therapeutic use
  • Hepatitis C / complications*
  • Hepatitis C / physiopathology
  • Humans
  • Liver / physiopathology*
  • Liver Function Tests
  • Lopinavir
  • Pyrimidinones / pharmacokinetics*
  • Pyrimidinones / therapeutic use
  • Ritonavir / pharmacokinetics*
  • Ritonavir / therapeutic use


  • HIV Protease Inhibitors
  • Pyrimidinones
  • Lopinavir
  • Ritonavir