Open AccessINFLUENCE OF LOVASTATIN ON PHARMACOKINETICS AND PHARMACODYNAMICS OF GLIPIZIDE IN HEALTHY AND STREPTOZOTOCIN - INDUCED DIABETIC RATS: INVOLVEMENT OF P-GLYCOPROTEIN INHIBITION
Author(s) -
Kishore Kumar Kadimpati,
Vanishree Sammeta,
Ravindra Babu Pingili,
Sujatha Sanneboina
Publication year - 2016
Publication title -
asian journal of pharmaceutical and clinical research
Language(s) - English
Resource type - Journals
eISSN - 2455-3891
pISSN - 0974-2441
DOI - 10.22159/ajpcr.2016.v9i5.1191
Subject(s) - glipizide , pharmacokinetics , lovastatin , pharmacodynamics , pharmacology , verapamil , p glycoprotein , dyslipidemia , diabetes mellitus , medicine , chemistry , endocrinology , cholesterol , biochemistry , antibiotics , calcium , multiple drug resistance
This study evaluated the effect of lovastatin (Lov) on the pharmacokinetics and pharmacodynamics of glipizide (Gpz) in healthy and streptozotocininduceddiabeticrats.In singledose study(SDS), blood samples werecollectedonthe 1st day, whereas in multiple dose study on the 15 day at0-12 hrs. Lov significantly altered the pharmacokinetic parameters at the dose of 15 mg/kg in SDS and multiple dose study. The C of Gpz wasincreased from 2.97 to 8.38 and 9.87 to 24.58 ng/mL in healthy and diabetic rats, respectively, in multiple dose study. Rat everted sacs were used tostudy the transport of Gpz in the presence of Lov and verapamil (P-glycoprotein [P-gp] inhibitor). The transport of Gpz from mucosal to the serosalsurface was significantly increased from 4.32 to 5.65 and 6.02 µg/mL in the presence of Lov and verapamil, respectively. The interaction between Lovand Gpz is due to P-gp and CYP2C9 inhibition.Keywords: Diabetes, Dyslipidemia, Glipizide, Lovastatin, P-glycoprotein.maxth