title: Lopinavir/ritonavir pharmacokinetics in HIV and hepatitis C virus co-infected patients without liver function impairment: influence of liver fibrosis.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Fundació Lluita contra la SIDA, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. jmolto@flsida.org
authors.forename: José
authors.initials: J
authors.lastname: Moltó
authors.forename: Marta
authors.initials: M
authors.lastname: Valle
authors.forename: Asunción
authors.initials: A
authors.lastname: Blanco
authors.forename: Eugenia
authors.initials: E
authors.lastname: Negredo
authors.forename: Meritxell
authors.initials: M
authors.lastname: DelaVarga
authors.forename: Cristina
authors.initials: C
authors.lastname: Miranda
authors.forename: José
authors.initials: J
authors.lastname: Miranda
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Josep
authors.initials: J
authors.lastname: Vilaró
authors.forename: Cristina
authors.initials: C
authors.lastname: Tural
authors.forename: Joan
authors.initials: J
authors.lastname: Costa
authors.forename: Manuel José
authors.initials: MJ
authors.lastname: Barbanoj
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
mesh_terms: D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006526:Hepatitis C / Q000150:complications* / Q000503:physiopathology; D006801:Humans; D008099:Liver / Q000503:physiopathology*; D008111:Liver Function Tests; D061466:Lopinavir; D011744:Pyrimidinones / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019438:Ritonavir / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir