| Autor: |
Wahajuddin, Satyendra Suryawanshi, Shio Kumar Singh, Ram Chandra Gupta |
| Rok vydání: |
2010 |
| Předmět: |
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| Zdroj: |
Journal of Pharmacy and Pharmacology. 63:41-48 |
| ISSN: |
0022-3573 |
| Popis: |
Objectives This manuscript addresses key pharmacokinetic issues in support of the development of a potent candidate lipid-lowering drug molecule, 16-dehydropregnenolone (DHP). Methods Liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) assay for simultaneous estimation of DHP and its metabolites, including 5-pregnene-3β-ol-16, 17-epoxi-20-one (M1) was validated in male and female Sprague–Dawley rat plasma and applied to different studies. Pharmacokinetic studies of DHP after intravenous and oral administration were carried out to assess any gender effect. Dose-proportionality after oral administration was assessed at three dose levels. Protein binding was estimated using the modified charcoal adsorption method. Key findings Rapid elimination of DHP from the systemic circulation resulted in a comparatively lesser systemic exposure in male compare to female rats. The area under the curve (AUC) after oral administration in males was significantly different tofemales. The large volume of distribution and low degree of protein binding suggest extensive distribution of DHP. An increase in the oral dose led to a disproportionate change in peak concentration (Cmax) and AUC, indicating variable absorption. However, the dose-normalized AUC and Cmax at two dose levels were not found to be statistically different. Conclusions The extent of conversion of DHP to M1 was higher after oral administration in male rats but was insignificant in female rats. DHP showed low systemic oral bioavailability and exhibited dose-independent pharmacokinetics and gender differences. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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