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BioMed Research International
Volume 2015 (2015), Article ID 517295, 7 pages
http://dx.doi.org/10.1155/2015/517295
Research Article

The Effect of MGCD0103 on CYP450 Isoforms Activity of Rats by Cocktail Method

1The Second Affiliated Hospital & Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325000, China
2Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China
3Medical Experimental Teaching Center, Wenzhou Medical University, Wenzhou 325035, China
4The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China

Received 19 February 2015; Revised 10 April 2015; Accepted 22 April 2015

Academic Editor: Wen-An Qiang

Copyright © 2015 Jinzhang Cai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

MGCD0103, an isotype-selective histone deacetylase inhibitor (HDACi), has been clinically evaluated for the treatment of hematologic malignancies and advanced solid tumors, alone and in combination with standard-of-care agents. In order to investigate the effects of MGCD0103 on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of human CYP2B1, CYP1A2, CYP2C11, CYP2D6, CYP3A4, and CYP2C9. The rats were randomly divided into MGCD0103 group (Low, Medium, and High) and control group. The MGCD0103 group rats were given 20, 40, and 80 mg/kg (Low, Medium, and High) MGCD0103 by continuous intragastric administration for 7 days. Six probe drugs, bupropion, phenacetin, tolbutamide, metoprolol, testosterone, and omeprazole, were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. Statistical pharmacokinetics difference for tolbutamide in rats were observed by comparing MGCD0103 group with control group. Continuous 7-day intragastric administration of MGCD0103 slightly induces the activities of CYP2C11 of rats.