title: Pharmacokinetics of verapamil in diabetic rats induced by combination of high-fat diet and streptozotocin injection.
abstract: The aim of this study was to investigate effects of type 2 diabetes on the pharmacokinetics of verapamil after intravenous administration. Diabetes mellitus (DM) rats were induced by combination of high-fat diet (HFD) and streptozotocin. Plasma concentrations of verapamil in DM rats, rats fed with HFD, and control (CON) rats were measured after intravenous administration of 1 mg/kg verapamil and corresponding pharmacokinetic parameters were estimated. Area under the plasma concentration in DM rats was significantly smaller than that in CON rats. In vitro microsomal study showed that intrinsic clearance of verapamil in DM rats was significantly higher than those in CON rats. Compared to CON rats, higher intrinsic clearance was also observed in HFD rats. Western blot results demonstrated higher levels of CYP3A2 in DM and HFD rats, which was in line to activity of CYP3A. All the results gave a conclusion that diabetes may enhance metabolism of verapamil in rat, and the enhancement may partly result from induction of CYP3A.
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
authors.forename: G M
authors.initials: GM
authors.lastname: Chen
authors.forename: N
authors.initials: N
authors.lastname: Hu
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: S S
authors.initials: SS
authors.lastname: Xie
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Xie
authors.forename: G J
authors.initials: GJ
authors.lastname: Wang
authors.forename: X D
authors.initials: XD
authors.lastname: Liu
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000378:metabolism*; D004032:Diet; D004041:Dietary Fats / Q000009:adverse effects; D004195:Disease Models, Animal; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000008:administration & dosage; D014700:Verapamil / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000889:Anti-Arrhythmia Agents; D004041:Dietary Fats; D013311:Streptozocin; D014700:Verapamil; D051544:Cytochrome P-450 CYP3A