Format

Send to

Choose Destination

See 1 citation found by title matching your search:

PLoS One. 2014 Apr 15;9(4):e94962. doi: 10.1371/journal.pone.0094962. eCollection 2014.

In vitro metabolism of 20(R)-25-methoxyl-dammarane-3, 12, 20-triol from Panax notoginseng in human, monkey, dog, rat, and mouse liver microsomes.

Author information

1
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
2
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, China.
3
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning, China; Key Laboratory of Research and Design of "Drug Targets Based on the Ministry of Education", Shenyang Pharmaceutical University, Shenyang, Liaoning, China.

Abstract

The present study characterized in vitro metabolites of 20(R)-25-methoxyl-dammarane-3β, 12β, 20-triol (20(R)-25-OCH3-PPD) in mouse, rat, dog, monkey and human liver microsomes. 20(R)-25-OCH3-PPD was incubated with liver microsomes in the presence of NADPH. The reaction mixtures and the metabolites were identified on the basis of their mass profiles using LC-Q/TOF and were quantified using triple quadrupole instrument by multiple reaction monitoring. A total of 7 metabolites (M1-M7) of the phase I metabolites were detected in all species. 25(R)-OCH3-PPD was metabolized by hydroxylation, dehydrogenation, and O-demethylation. Enzyme kinetic of 20(R)-25-OCH3-PPD metabolism was evaluated in rat and human hepatic microsomes. Incubations studies with selective chemical inhibitors demonstrated that the metabolism of 20(R)-25-OCH3-PPD was primarily mediated by CYP3A4. We conclude that 20(R)-25-OCH3-PPD was metabolized extensively in mammalian species of mouse, rat, dog, monkey, and human. CYP3A4-catalyzed oxygenation metabolism played an important role in the disposition of 25(R)-OCH3-PPD, especially at the C-20 hydroxyl group.

PMID:
24736630
PMCID:
PMC3988085
DOI:
10.1371/journal.pone.0094962
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center