Effect of esomeprazole on the pharmacokinetics of carbamazepine

OBJECTIVE: Present study was carried out to evaluate effect of esomeprazole on the pharmacokinetics of carbamazepine in rabbits. MATERIALS AND METHODS: Study was conducted at Department of Pharmacology, Postgraduate Institute of Medical Education and Research from March to October 2007. In a parallel design study, carbamazepine 40 mg/kg/day was given orally for 14 days. On day 15, blood samples were taken at various time intervals between 0 and 24 hours. In esomeprazole group, carbamazepine was administered for 14 days as above. On day 8, esomeprazole 2.8 mg/kg/day along with carbamazepine 40 mg/kg/day was administered till 14 days and blood samples were drawn on 15(th) day. Plasma levels of carbamazepine were assayed by high-performance liquid chromatography and pharmacokinetic parameters were calculated. RESULTS: In all groups there was a decrease in the AUC(0-24) when carbamazepine was coadministered with esomeprazole. The decrease in AUC(0-24) (22.78 ± 4.71 to 10.46 ± 2.29), C(max) (2.76 ± 0.77 to 1.412±1.08), T(max) (2.83 ± 0.17 to 3 ± 0.40) was statistically significant (P < 0.05) when esomeprazole was given along with carbamazepine. Additionally, absorption and elimination constant were also altered significantly. CONCLUSIONS: These results suggest that concomitant use of esomeprazole alters the pharmacokinetics of carbamazepine. Confirmation of these results in human studies will warrant changes in carbamazepine dose or frequency when esomeprazole is coadministered.