Data/hora: 05/06/2024 18:24:07

Provedor de dados: | 56
País: | Brazil
Título: | A new model for the population pharmacokinetics of didanosine in healthy subjects
Autores: | Velasque,L.S.; Estrela,R.C.E.; Suarez-Kurtz,G.; Struchiner,C.J.
Data: | 2007-01-01
Ano: | 2007
Palavras-chave: | Didanosine; Pharmacokinetics; NONMEM.
Resumo: | Didanosine (ddI) is a component of highly active antiretroviral therapy drug combinations, used especially in resource-limited settings and in zidovudine-resistant patients. The population pharmacokinetics of ddI was evaluated in 48 healthy volunteers enrolled in two bioequivalence studies. These data, along with a set of co-variates, were the subject of a nonlinear mixed-effect modeling analysis using the NONMEM program. A two-compartment model with first order absorption (ADVAN3 TRANS3) was fitted to the serum ddI concentration data. Final pharmacokinetic parameters, expressed as functions of the co-variates gender and creatinine clearance (CL CR), were: oral clearance (CL = 55.1 + 240 x CL CR + 16.6 L/h for males and CL = 55.1 + 240 x CL CR for females), central volume (V2 = 9.8 L), intercompartmental clearance (Q = 40.9 L/h), peripheral volume (V3 = 62.7 + 22.9 L for males and V3 = 62.7 L for females), absorption rate constant (Ka = 1.51/h), and dissolution time of the tablet (D = 0.43 h). The intraindividual (residual) variability expressed as coefficient of variation was 13.0%, whereas the interindividual variability of CL, Q, V3, Ka, and D was 20.1, 75.8, 20.6, 18.9, and 38.2%, respectively. The relatively high (&gt;30%) interindividual variability for some of these parameters, observed under the controlled experimental settings of bioequivalence trials in healthy volunteers, may result from genetic variability of the processes involved in ddI absorption and disposition.
Tipo: | Info:eu-repo/semantics/article
Idioma: | Inglês
Identificador: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2007000100013
Editor: | Associação Brasileira de Divulgação Científica
Relação: | 10.1590/S0100-879X2006005000048
Formato: | text/html
Fonte: | Brazilian Journal of Medical and Biological Research  v.40 n.1 2007
Fonte: | info:eu-repo/semantics/openAccess