INFLUENCE OF LOVASTATIN ON PHARMACOKINETICS AND PHARMACODYNAMICS OF GLIPIZIDE IN HEALTHY AND STREPTOZOTOCIN - INDUCED DIABETIC RATS: INVOLVEMENT OF P-GLYCOPROTEIN INHIBITION

This study evaluated the effect of lovastatin (Lov) on the pharmacokinetics and pharmacodynamics of glipizide (Gpz) in healthy and streptozotocininduced diabetic rats. In single dose study (SDS), blood samples were collected on the 1st day, whereas in multiple dose study on the 15th day at 0-12 hrs. Lov significantly altered the pharmacokinetic parameters at the dose of 15 mg/kg in SDS and multiple dose study. The Cmax of Gpz was increased 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 to study the transport of Gpz in the presence of Lov and verapamil (P-glycoprotein [P-gp] inhibitor). The transport of Gpz from mucosal to the serosal surface 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 Lov and Gpz is due to P-gp and CYP2C9 inhibition. Keywords: Diabetes, Dyslipidemia, Glipizide, Lovastatin, P-glycoprotein.