Caffeine modulates pharmacokinetic and pharmacodynamic profiles of pioglitazone in diabetic rats : Impact on therapeutics

Abstract

Objectives:

To determine the influence of caffeine on pharmacokinetics and pharmacodynamics of pioglitazone (PIO) in diabetic rats.

Methods:

This was a preclinical study conducted in the College of Pharmacy, Najran University, Saudi Arabia, using 5 groups of Wistar rats: normal rats, untreated diabetic rats, diabetic rats + caffeine (20 mg/kg), diabetic rats + PIO (10 mg/kg), and diabetic rats + PIO (10 mg/kg) + caffeine (20 mg/kg). The drugs were administered for 14 days, and fasting plasma glucose concentrations were determined on the first day, and thereafter at weekly intervals. On day 14, rat sacrifice was followed with assay of levels of biomarkers. To estimate the pharmacokinetic parameters, the diabetic animals were assigned to 2 groups: one group received PIO (10 mg/kg), while the other received PIO + caffeine (20 mg/kg). Blood samples were drawn from the retro-orbital plexus at different time intervals, and pharmacokinetic parameters were measured using high performance liquid chromatography.

Results:

Caffeine caused statistically marked increases in area under the curve, C _max, T _max, and half-life of PIO, and decreased clearance. Combination of PIO and caffeine produced a synergistic effect on percentage reduction in blood glucose, with 67.1% reductions observed on day 7 and 68.9% reductions observed on day 14. Liver and cardiac biomarkers were significantly decreased, suggesting cardioprotective and hepatoprotective effects.

Conclusion:

Co-administration of PIO with caffeine enhances its antidiabetic effect, probably due to enhanced bioavailability of PIO, leading to clinical benefits in diabetic patients.