Lack of an effect of human immunodeficiency virus coinfection on the pharmacokinetics of entecavir in hepatitis B virus-infected patients.

Abstract

Entecavir is a guanosine nucleoside analogue approved for the treatment of chronic hepatitis B virus (HBV) infection. The impact of human immunodeficiency virus (HIV) coinfection on the pharmacokinetics (PK) of entecavir was examined by nonlinear mixed-effects modeling. Plasma concentration data from HIV- and HBV-coinfected patients were analyzed in conjunction with data from HBV-monoinfected patients, and HIV coinfection was tested as a covariate on oral clearance (CL/F). The estimated population averages of intercompartmental clearance and the volumes of distribution in the central and peripheral compartments obtained with a 1-mg dose were 34.2 liters/h (interindividual variability, 30.2%), 115 liters (interindividual variability, 39.2%), and 1,830 liters (interindividual variability, 74%), respectively. CL/F was found to be a function of creatinine clearance, but HIV confection did not show any effect on CL/F. The geometric mean (GM) of individual Bayesian estimates of the steady-state area under the concentration-time curve following 1-mg daily doses were 39.3 and 38.8 ng x h/ml in HIV- and HBV-coinfected and HBV-monoinfected patients, respectively. The adjusted GM ratio (1.01; 90% confidence interval, 0.91 to 1.12) was within the bioequivalence criteria boundary (0.80 to 1.25). In conclusion, the proposed model adequately described the entecavir PK in HBV- and HIV-coinfected patients and HBV-monoinfected patients, and the entecavir exposures were comparable in the two patient populations.

• Authors: Min Zhu, Marc Bifano, Xu Xu, Yonghua Wang, Frank LaCreta, Dennis Grasela, Marc Pfister
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 52 Issue 8 Pg. 2836-41 (Aug 2008) ISSN: 1098-6596 [Electronic] United States
• PMID: 18391039 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Antiviral Agents
• entecavir
• Guanine

Topics

• Algorithms
• Antiviral Agents (pharmacokinetics, therapeutic use)
• Area Under Curve
• Guanine (analogs & derivatives, blood, pharmacokinetics, therapeutic use)
• HIV Infections (complications, drug therapy)
• Hepatitis B (complications, drug therapy)
• Humans
• Metabolic Clearance Rate
• Models, Biological
• Randomized Controlled Trials as Topic