Kavalactone Metabolism in Rat Liver Microsomes
Article first published online: 22 DEC 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Volume 26, Issue 7, pages 1057–1061, July 2012
How to Cite
Fu, S., Rowe, A. and Ramzan, I. (2012), Kavalactone Metabolism in Rat Liver Microsomes. Phytother. Res., 26: 1057–1061. doi: 10.1002/ptr.3695
- Issue published online: 5 JUL 2012
- Article first published online: 22 DEC 2011
- Manuscript Accepted: 29 SEP 2011
- Manuscript Revised: 1 SEP 2011
- Manuscript Received: 27 JUN 2011
- cytochrome P450;
The specific CYP enzymes involved in kavalactone (KLT) metabolism and their kinetics have not been fully examined. This study used rat liver microsomes (RLM) to determine kavain (KA), methysticin (MTS) and desmethoxyyangonin (DMY) enzyme kinetic parameters, to elucidate the major CYP450 isoforms involved in KLT metabolism and to examine gender differences in KLT metabolism. Formation of the major KLT metabolites was first-order, consistent with classic enzyme kinetics. In both male and female RLM, clotrimazole (CLO) was the most potent inhibitor of KA and MTS metabolism. This suggests CYP3A1/3A23 (females) and CYP3A2 (males) are the main isoenzymes involved in the metabolism of these KLTs in rats, while the roles of CYP1A2, -2 C6, -2 C9, -2E1 and -3A4 are limited. Desmethoxyyangonin metabolism was equally inhibited by cimetidine (CIM) and CLO in females, and CIM and nortriptyline in males. This implies that DMY metabolism involves CYP2C6 and CYP2C11 in males, and CPY2C12 in females. CYP3A1/3A23 may also be involved in females. Copyright © 2011 John Wiley & Sons, Ltd.