jdm

Journal of Diabetes & Metabolism

ISSN - 2155-6156

Abstract

Influence of Piperine on Pioglitazone Metabolism and Pk/Pd: Diabetes Mellitus

Prasad Neerati

Background: Piperine is an alkaloidal compound and is an active constituent of black and long peppers. Piperine is known to inhibit cytochrome P- 450 isoforms. The objective was to determine the effects of dietary piperine on the pharmacokinetics and pharmacodynamics of pioglitazone.

Methods and Results: Set one non diabetic study, there are three groups, as 1,2 and 3 composed each of four Albino rabbits (2-3 kg). In the next set, another similar three groups named group 4 group 5 and group 6 were selected to investigate the influences in diabetic group after receiving alloxan monohydrate (80 mg/kg, i.v). Group 1 and group 2; group 4 and group 5 received pioglitazone (10 mg/kg; po) and piperine (20 mg/kg; po) respectively. Group 3 and group 6, we investigated herb drug interactions for single dose and multiple dose interactions on normal and diabetic rabbits with piperine for single day and for eight days. On the last day of piperine pre-treatment, pioglitazone was given. 1 ml blood samples collected intravenously via marginal ear vein, at the pre set time points and PK & PD parameters were measured. Serum levels of pioglitazone measured using RP-HPLC and glucose levels measured. Significant changes observed under multiple dose pre-treatment of piperine. AUCtot of pioglitazone significantly increased in normal and diabetic rabbits. The biological half-life (t1/2) was increased whereas clearance was decreased. Maximum percentage glucose reduction was increased significantly in both single and multiple dose pre-treatment of piperine in diabetic rabbits. The observations suggest an interaction due to metabolic inhibition of CYP enzymes.

Conclusion: Piperine increases the bioavailability of pioglitazone in normal and diabetic rabbits. Piperine, pioglitazone combination has a beneficial effect in diabetes but it may require special care and should be given under medical supervision with appropriate dose combinations in severe diabetes.

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