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 In recent years, several drugs have been withdrawn from the market due to interaction-related adverse events.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 C(max), T(max), t (1/2), AUC(0-t), AUC (0-∞), and k(e) were determined for the two periods using non-compartmental analysis. RESULTS: In the two periods of treatment, C(max), T(max), AUC(0-t), AUC(0-∞), t (½) and k(e) for CBZ were administered alone and in combination with PG. C(max), the mean peak plasma concentration was 4.33 ± 2.4 μg/mL versus 4.76 ± 2.1 μg/ml, t(max), time taken to reach, was 2.91 ± 1.11 h versus 3.6 ± 1.83 h, total area under the curve AUC(0-t) was 64.90 ± 43.6 μg·h/ml versus 102.90 ± 66.9 μg·h/ml, AUC(0-∞) 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 k(e) 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.