Pharmacokinetics of Schizandrin and Metabolic Gender Differences in Rats.
|
Accession number;01A0649636
|
| Title;Pharmacokinetics of Schizandrin and Metabolic Gender Differences in Rats. |
| Author;
ONO H
(Tsumura & Co.)
|
Journal Title;Journal of the Medical Society of Toho University
|
Journal Code:G0654A
|
ISSN:0040-8670
|
|
VOL.48;NO.2;PAGE.125-139(2001)
|
| Figure&Table&Reference;FIG.8, TBL.4, REF.17 |
| Pub. Country;Japan |
| Language;English |
| Abstract;The pharmacokinetics and metabolism of schizandrin (SZ), a principal component of Schizandra chinensis BAILL prescribed in some traditional herbal medicines, were studied in rats following intravenous and oral administration of 14C-labeled schizandrin (14C-SZ). It was suggested that SZ administered orally was absorbed at more than 90% and rapidly distributed throughout the body. A significant amount of radioactivity was distributed to the liver, but little (less than 10% of the plasma level) was found in the central nervous system. After oral administration of 14C-SZ, most of the radioactivity (85%) was recovered in the bile with renal excretion accounting for only a small proportion (7%). These results indicate that biliary excretion was the primary route of elimination of SZ or its metabolites. Though the pharmacokinetics of SZ-related radioactivity was fundamentally the same in each sex, there were gender differences in the plasma concentration-time profile, tissue distribution and ratio of excretion into urine and feces. After intravenous administration of unlabeled SZ, the elimination of SZ was faster in male than female rats. A gender difference was also observed in the plasma concentration of metabolites, SZ-M4 being the major metabolite in male rats and SZ-MD1 in female rats. Similar results were obtained in vitro using hepatic microsomes from both sexes and the reactions required NADPH as a cofactor. The results suggest that the biotransformed products of SZ are produced by O-demethylation after monohydroxylation with the possible involvement of cytochrome P-450 systems. The gender difference in the pharmacokinetics of SZ in rats would be due to male dominant metabolic activity catalyzed by cytochrome P-450. The gender difference in the distribution of SZ would lead to the gender difference in pharmacological effects. (author abst.) |
|
|
|
Related Articles;
|
|
