The effect of pioglitazone on pharmacokinetics of carbamazepine in healthy rabbits.

INTRODUCTION

Drug-drug interactions can lead to serious and potentially lethal adverse events. In recent years, several drugs have been withdrawn from the market due to interaction-related adverse events. The objective of this study was to evaluate the pharmacokinetic interaction between pioglitazone (PG) and carbamazepine (CBZ) in healthy male rabbits.

METHODS

A randomized, two-crossover design study was conducted in six healthy male rabbits. The study consisted of two periods: period one, when each rabbit received a single dose of 70 mg CBZ-suspension. Period two, when each rabbit received a single dose of 70 mg CBZ-suspension co-administered with a single dose of 1.5 mg PG with a washout period of one week between the two periods. Serial blood samples were collected over a period of 48 h. Chemiluminescent enzyme immunoassay (CLEIA) was used to measure CBZ in serum. Pharmacokinetic (PK) parameters Cmax, Tmax, t 1/2, AUC0-t, AUC 0-∞, and ke were determined for the two periods using non-compartmental analysis.

RESULTS

In the two periods of treatment, Cmax, Tmax, AUC0-t, AUC0-∞, t ½ and ke for CBZ were administered alone and in combination with PG. Cmax, the mean peak plasma concentration was 4.33 ± 2.4 μg/mL versus 4.76 ± 2.1 μg/ml, tmax, time taken to reach, was 2.91 ± 1.11 h versus 3.6 ± 1.83 h, total area under the curve AUC0-t was 64.90 ± 43.6 μg·h/ml versus 102.90 ± 66.9 μg·h/ml, AUC0-∞ was 74.0 ± 52.6 μg·h/ml versus 124.3 ± 85 μg·h/mL, t ½ was 14.10 ± 2.5 h versus 16.43 ± 6.43 h and elimination rate constant ke was 0.050 ± 0.009 h(-1) versus 0.057 ± 0.049 h(-1), respectively. No statistical differences were found in pharmacokinetic of CBZ in both cases (P > 0.05).

CONCLUSION

The result of the study demonstrated that PG does not affect pharmacokinetic parameters of CBZ. Therefore, no cautions regarding dose or administration pattern of CBZ with PG should be taken.