Population pharmacokinetics of tenofovir in HIV-infected patients taking highly active antiretroviral therapy.

V. Jullien(1), J.M. Tréluyer(1), E. Rey(1), P. Jaffray(1), A. Krivine(1), L. Moachon(1), A Lillo-Le Louet(2), A. Lescoat(1), N. Dupin(1), D. Salmon(1), G. Pons(1), S. Urien(1).

(1)Université René Descartes, Groupe Hospitalier Cochin-Saint-Vincent-de-Paul, Paris, France. (2)Hôpital Européen Georges Pompidou, Paris, France.

Objectives: This study was performed to investigate the influence of renal function on tenofovir pharmacokinetics in HIV-infected adults with creatinine clearance higher than 50 mL/min.

Methods: A population pharmacokinetic model for tenofovir was developed from 193 adult patients by the use of a non-linear mixed effects modelling method performed with NONMEM.

Results: Tenofovir pharmacokinetics was well described by a two compartment open model in which the absorption rate constant was set to the distribution rate constant. Typical population estimates of apparent central distribution volume (Vc/F), peripheral distribution volume (Vp/F), intercompartmental clearance (Q/F) and plasma clearance (CL/F) were 534 L, 1530 L, 144 L/h and 90.9 L/h respectively. Apparent plasma clearance was related to bodyweight/serum creatinine ratio (BW/SCR) and to the existence of a tubular dysfunction. Concomitant treatment with lopinavir/ritonavir was found to decrease tenofovir clearance. Individual Bayesian estimates of CL/F were used to calculate the tenofovir area under the concentration-time curve from time zero to 24 h (AUC). In patients without tubular dysfunction, AUC values markedly decreased from 6.7 to 1.4 mg.h/L for BW/SCR increasing from 0.44 to 1.73.

Conclusion: BW/SCR was identified as a predictive factor of tenofovir AUC in HIV-infected patients. The relevance of a dosage adjustment based on BW/SCR should be further evaluated.

Reference: PAGE 14 (2005) Abstr 718 [www.page-meeting.org/?abstract=718]

Poster: poster