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16048948

Source:http://linkedlifedata.com/resource/pubmed/id/16048948

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pubmed-article:16048948pubmed:abstractTextThe 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 297 +/- 28.5 [corrected] liters, 848 +/- 209 [corrected] liters, 80 +/- 15 [corrected] liters/h and 50.5 +/- 3.1 [corrected] 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.lld:pubmed
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pubmed-article:16048948pubmed:articleTitlePopulation pharmacokinetics of tenofovir in human immunodeficiency virus-infected patients taking highly active antiretroviral therapy.lld:pubmed
pubmed-article:16048948pubmed:affiliationService de Pharmacologie Clinique, Hôpital Cochin-Saint-Vincent-de-Paul, 74-82 Avenue Denfert-Rochereau, 75674 Paris Cedex 14, France. Vincent.jullien@svp.aphp.frlld:pubmed
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pubmed-article:16048948pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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