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Pharmacokinetics of progesterone in lactating dairy cows: gaining some insights into the metabolism from kinetic modeling.
Turino, L N; Mariano, R N; Cabrera, M I; Scándolo, D E; Maciel, M G; Grau, R J A.
Afiliação
  • Turino LN; Laboratorio de Química Fina, Instituto de Desarrollo Tecnológico para la Industria Química (INTEC), Universidad Nacional del Litoral, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Predio CCT-CONICET Santa Fe, Santa Fe, Argentina.
J Dairy Sci ; 93(3): 988-99, 2010 Mar.
Article em En | MEDLINE | ID: mdl-20172219
Progesterone pharmacokinetics were analyzed for plasma hormone concentrations ranging from linear to saturated metabolism in lactating Holstein cows with differing daily milk yields. The adequacy of 2-coupled first-order (bi-exponential equation), hyperbolic (Michaelis-Menten equation), and sigmoidal (Hill equation) kinetic models to describe the experimental progesterone pharmacokinetic profiles was examined on a statistical basis. After nonlinear regression and statistical analysis of the data-fitting capability, a simple one-compartment model based on Hill equation proved to be most adequate. This model indicates an enzyme-catalyzed metabolism of progesterone involving cooperative substrate-binding sites, resulting from allosteric effects that yield a sigmoidal saturation rate curve. Kinetic parameters were estimated for 2 groups of lactating Holstein cows with different daily milk yields. We found, for the first time, a remarkable quantitative agreement of the Hill coefficient value with that reported in pharmacokinetic studies involving cytochrome P450, family 3, subfamily A (CYP3A)-mediated reactions in other mammals, humans included. It seems that positive cooperativity makes enzymes much more sensitive to plasma progesterone concentration, and their activities can undergo significant changes in a narrow range of concentration as characteristic of sigmoidal behavior. Therefore, the values of classical pharmacokinetic parameters, such as the elimination constant, half-life, and clearance rate, were found to be highly dependent on the plasma progesterone concentration.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Progestinas / Progesterona / Lactação / Bovinos Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals Idioma: En Revista: J Dairy Sci Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Progestinas / Progesterona / Lactação / Bovinos Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals Idioma: En Revista: J Dairy Sci Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos