Population pharmacokinetics of tenofovir in human immunodeficiency virus-infected patients taking highly active antiretroviral therapy
Population pharmacokinetics of tenofovir in human immunodeficiency virus-infected patients taking highly active antiretroviral therapy
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DOI：
10.1128/aac.49.8.3361-3366.2005
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发表时间：
2005-08-01
影响因子：
4.9
通讯作者：
Urien, S
中科院分区：
文献类型：
--
作者：
Jullien, V;Tréluyer, JM;Urien, S
The influence of renal function on tenofovir pharmacokinetics was investigated in 193 human immunodeficiency virus (HIV)-infected patients by the use of a population approach performed with the nonlinear mixed effects modeling program NONMEM. Tenofovir pharmacokinetics was well described by a two-compartment open model in which the absorption and the distribution rate constants are equal. Typical population estimates of apparent central distribution volume (V-c/F), peripheral distribution volume (V-p/F), intercompartmental clearance (Q/F), and plasma clearance (CL/F) were 534 liters, 1,530 liters, 144 liters/h and 90.9 liters/h, respectively. Apparent plasma clearance was related to body weight/serum creatinine ratio (BW/S-CR) 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(0-24)). In patients without tubular dysfunction, AUC(0-24), values markedly decreased from 6.7 to 1.4 mg (.) h/liter for BW/S-CR increasing from 0.44 to 1.73. The relevance of a dosage adjustment based on BW/S-CR should be further evaluated.
