Authors: Moltó, José; Valle, Marta; Blanco, Asunción¹; Negredo, Eugenia²; DelaVarga, Meritxell¹; Miranda, Cristina²; Miranda, José²; Domingo, Pere³; Vilaró, Josep⁴; Tural, Cristina²; Costa, Joan⁵; Barbanoj, Manuel José; Clotet, Bonaventura

Source: Clinical Pharmacokinetics, Volume 46, Number 1, 2007 , pp. 85-92(8)

Publisher: Adis International

Abstract:

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 (400mg/100mg 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 (C_max and C_min), area under the plasma concentration-time curve from 0 to 12 hours (AUC₁₂), apparent oral clearance at steady state (CL_ss/F), and apparent volume of distribution after oral administration (V_d/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 V_d/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 CL_ss/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, C_max and C_min 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.

Keywords: Antiretrovirals; Hepatitis C; HIV infections; HIV protease inhibitors; Lopinavir/ritonavir

Document Type: Research article

Affiliations: 1: 4 Fundació “IrsiCaixa”, Hospital Universitari Germans Trias i Pujol, Badalona, Spain 2: 1 Fundació “Lluita contra la SIDA”, Hospital Universitari Germans Trias i Pujol, Badalona, Spain 3: 5 Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain 4: 6 Department of Internal Medicine, Hospital de Vic, Vic, Spain 5: 7 Department of Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain

Publication date: 2007-01-01

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• By this author: Moltó, José ;  Valle, Marta ;  Blanco, Asunción ;  Negredo, Eugenia ;  DelaVarga, Meritxell ;  Miranda, Cristina ;  Miranda, José ;  Domingo, Pere ;  Vilaró, Josep ;  Tural, Cristina ;  Costa, Joan ;  Barbanoj, Manuel José ;  Clotet, Bonaventura

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