Journal of Clinical & Experimental Pharmacology

Effects of cytochrome P450 (CYP)2D6 inhibitions in in vivo toxicity studies of mitragynine

Co-organized Event International Conference on Toxicology and Clinical Pharmacology & 2^nd International Conference on Generic Drugs and Biosimilars

December 14-16, 2017 Rome, Italy

Zamri Chik

University of Malaya, Malaysia

Scientific Tracks Abstracts: Clin Exp Pharmacol

Abstract:

Mitragynine, the most abundant active component found in the leaves of Mitragyna speciosa, has been proposed to use as pain and opiate withdrawal symptoms reliever. Even though it had been banned in certain countries, however, some people still consume it for different medical indications. In recent years, it has been strongly related to drug abused and several reported death cases. In our study, the effects of CYP2D6 on mitragynineâ??s metabolism and drug-drug interaction (DDI)-induced toxicity were investigated intensively using quinidine, a CYP2D6 inhibitor. The findings showed that coadministration of 10 mg/kg quinidine increased the mitragynine elimination half-life and area under the curve significantly using a conventional pharmacokinetic study. The experiment was extended with in vivo 14-days toxicity study at highest dose 50 mg/kg of mitragynine. Lethal dose of 300 mg/kg mitragynine alone was identified in the pilot study. Whereas, mortality rate of mitragynine (4 out of 6 rats) at 50 mg/kg was dramatically increased in the presence of quinidine as compared with mitragynine control. Liver markers such as AST and ALT were also significantly elevated at the dose as low as 5 mg/kg with quinidine co-administration. Lastly, histopathological analysis showed inflammatory cell infiltration in both of liver and kidney at highest tested dose. In conclusion, CYP2D6 plays the major role in phase I metabolism of mitragynine and it strongly associated with the DDI-induced mortality, as well as hepatotoxicity. Therefore, concurrent administration of mitragynine and drugs which are inhibitors of the CYP2D6 enzyme would increase fatality among mitragynine consumers or abusers.

Biography :

Zamri Chik completed his PhD in Clinical Pharmacology from the University of London, UK in 2007. He later joined the Department of Pharmacology, University of Malaya and promoted to Associate Professor in 2015 and currently serves as a Head of Department. His scope of research includes bioavailability and pharmacokinetic studies in human and animal models. His other research includes the development of transdermal and topical drug delivery system using semi solid base such as palm oil derivatives and PLGA nanoparticles. Apart from human trials and preclinical studies in animals, his research also covers the screening and testing of natural product compounds derive from selected local plants. He also actively provided consultation to pharmaceutical companies to conduct bioequivalence testing for generic drug products. He has over 30 publications that has been cited over 100 times and has been serving as a reviewer in various reputable journals.