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

## TL;DR

This study examines how MGCD0103 affects rat CYP450 enzyme activity using a cocktail method to assess drug metabolism.

## Contribution

The study reveals that MGCD0103 slightly induces CYP2C11 activity in rats after 7 days of administration.

## Key findings

- MGCD0103 slightly induces CYP2C11 activity in rats.
- Statistical differences in tolbutamide pharmacokinetics were observed between MGCD0103-treated and control rats.

## 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.