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Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling.
- Source :
-
Journal of Dairy Science . Mar2010, Vol. 93 Issue 3, p988-999. 12p. 1 Diagram, 5 Charts, 4 Graphs. - Publication Year :
- 2010
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PHARMACOKINETICS
*PROGESTERONE
*METABOLISM
*MILKING
*QUANTITATIVE research
*COWS
Subjects
Details
- Language :
- English
- ISSN :
- 00220302
- Volume :
- 93
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of Dairy Science
- Publication Type :
- Academic Journal
- Accession number :
- 48575469
- Full Text :
- https://doi.org/10.3168/jds.2009-2519