Data/hora: 01/06/2024 01:12:23

Provedor de dados: | 56
País: | Brazil
Título: | Limited-sampling strategy models for estimating the pharmacokinetic parameters of 4-methylaminoantipyrine, an active metabolite of dipyrone
Autores: | Suarez-Kurtz,G.; Ribeiro,F.M.; Estrela,R.C.E.; Vicente,F.L.; Struchiner,C.J.
Data: | 2001-11-01
Ano: | 2001
Palavras-chave: | Dipyrone; 4-methylaminoantipyrine; Limited-sampling models; Pharmacokinetics; Bioequivalence.
Resumo: | Bioanalytical data from a bioequivalence study were used to develop limited-sampling strategy (LSS) models for estimating the area under the plasma concentration versus time curve (AUC) and the peak plasma concentration (Cmax) of 4-methylaminoantipyrine (MAA), an active metabolite of dipyrone. Twelve healthy adult male volunteers received single 600 mg oral doses of dipyrone in two formulations at a 7-day interval in a randomized, crossover protocol. Plasma concentrations of MAA (N = 336), measured by HPLC, were used to develop LSS models. Linear regression analysis and a "jack-knife" validation procedure revealed that the AUC0-&lt;FONT FACE=Symbol&gt;¥&lt;/FONT&gt; and the Cmax of MAA can be accurately predicted (R²&gt;0.95, bias &lt;1.5%, precision between 3.1 and 8.3%) by LSS models based on two sampling times. Validation tests indicate that the most informative 2-point LSS models developed for one formulation provide good estimates (R²&gt;0.85) of the AUC0-&lt;FONT FACE=Symbol&gt;¥&lt;/FONT&gt; or Cmax for the other formulation. LSS models based on three sampling points (1.5, 4 and 24 h), but using different coefficients for AUC0-&lt;FONT FACE=Symbol&gt;¥&lt;/FONT&gt; and Cmax, predicted the individual values of both parameters for the enrolled volunteers (R²&gt;0.88, bias = -0.65 and -0.37%, precision = 4.3 and 7.4%) as well as for plasma concentration data sets generated by simulation (R²&gt;0.88, bias = -1.9 and 8.5%, precision = 5.2 and 8.7%). Bioequivalence assessment of the dipyrone formulations based on the 90% confidence interval of log-transformed AUC0-&lt;FONT FACE=Symbol&gt;¥&lt;/FONT&gt; and Cmax provided similar results when either the best-estimated or the LSS-derived metrics were used.
Tipo: | Info:eu-repo/semantics/article
Idioma: | Inglês
Identificador: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2001001100017
Editor: | Associação Brasileira de Divulgação Científica
Relação: | 10.1590/S0100-879X2001001100017
Formato: | text/html
Fonte: | Brazilian Journal of Medical and Biological Research  v.34 n.11 2001
Fonte: | info:eu-repo/semantics/openAccess