| First Author | Shi C | Year | 2017 |
| Journal | Basic Clin Pharmacol Toxicol | Volume | 121 |
| Issue | 3 | Pages | 169-174 |
| PubMed ID | 28374976 | Mgi Jnum | J:277528 |
| Mgi Id | MGI:6296275 | Doi | 10.1111/bcpt.12794 |
| Citation | Shi C, et al. (2017) Peroxisome Proliferator-Activated Receptor alpha Activation Suppresses Cytochrome P450 Induction Potential in Mice Treated with Gemfibrozil. Basic Clin Pharmacol Toxicol 121(3):169-174 |
| abstractText | Gemfibrozil, a peroxisome proliferator-activated receptor alpha (PPARalpha) agonist, is widely used for hypertriglyceridaemia and mixed hyperlipidaemia. Drug-drug interaction of gemfibrozil and other PPARalpha agonists has been reported. However, the role of PPARalpha in cytochrome P450 (CYP) induction by fibrates is not well known. In this study, wild-type mice were first fed gemfibrozil-containing diets (0.375%, 0.75% and 1.5%) for 14 days to establish a dose-response relationship for CYP induction. Then, wild-type mice and Pparalpha-null mice were treated with a 0.75% gemfibrozil-containing diet for 7 days. CYP3a, CYP2b and CYP2c were induced in a dose-dependent manner by gemfibrozil. In Pparalpha-null mice, their mRNA level, protein level and activity were induced more than those in wild-type mice. So, gemfibrozil induced CYP, and this action was inhibited by activated PPARalpha. These data suggested that the induction potential of CYPs was suppressed by activated PPARalpha, showing a potential role of this receptor in drug-drug interactions and metabolic diseases treated with fibrates. |
