| Registro completo |
| Provedor de dados: |
BJMBR
|
| 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-<FONT FACE=Symbol>¥</FONT> and the Cmax of MAA can be accurately predicted (R²>0.95, bias <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>0.85) of the AUC0-<FONT FACE=Symbol>¥</FONT> 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-<FONT FACE=Symbol>¥</FONT> and Cmax, predicted the individual values of both parameters for the enrolled volunteers (R²>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>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-<FONT FACE=Symbol>¥</FONT> 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
|
| Direitos: |
info:eu-repo/semantics/openAccess
|
|
