The effect of norfloxacin on pharmacokinetics of carbamazepine at steady state in rabbits
Journal Title: Journal of Pharmaceutical and Biological Sciences - Year 2017, Vol 5, Issue 5
Abstract
Introduction: Carbamazepine (CBZ) is one of the most commonly prescribed antiepileptic drugs. Carbamazepine is rapidly absorbed with a bioavailability of 75.85% with plasma protein binding of 75%. It is extensively metabolized in the liver, primarily by CYP3A4, to carbamazepine-10, 11-epoxide. CBZ initial half-life elimination values ranges from 25-65 hours, decreasing to 12-24 hours on repeated doses, because of autoinduciton effect. Metabolism of drugs by cytochrome system can lead to several drug-drug interactions, which result in decrease pharmacological action, drug toxicity and adverse drug reactions. Norfloxacin (NFX) is an antibiotic, which exhibited a moderate CYP3A4 inhibitory effect. The aim of this study was to investigate the effect of NFX on pharmacokinetics of CBZ at steady state in rabbits. Materials and Method: An in vivo drug-drug interaction, a randomized, crossover design study was conducted in six healthy male rabbits between NFX and CBZ. The study was carried out on two periods, first period (CBZ) was administered alone as daily single oral dose (40 mg/kg) for 10 days. In the second period, CBZ was administered as a single oral dose (40 mg/kg) for three consecutive days. On the fourth day a single dose of NFX (11.4 mg/kg) was given orally along with CBZ for the following seven days to each rabbit, after a washout period (10 days). Serial blood samples were collected over a period of 24 hours after the last dose of CBZ. Chemiluminescent enzyme immunoassay (CLEIA) was used to measure CBZ concentration in serum. Pharmacokinetic parameters as Cmax, tmax AUC 0-24 , AUC 0-∞ , t1/2 and the constant rate of elimination Ke were determined for the two periods. Results: Six rabbits were enrolled in the study which exhibited good tolerability to CBZ and NFX formulations. No statistical differences were found based on ANOVA between the two periods. The mean values of PK parameters for first and second periods were as follows: Cmax= 9.970 versus 8.400 µg/ml, AUC 0- ∞= 154.1 versus 166.8 µg.h/ml, AUC 0-24= 130.3 versus 113.6 µg.h/ml, ke= 0.0587 versus 0.0419 h-1, tmax= 4.330 versus 4.580 h and t½= 12.78 versus 21.34 h for the first and second periods, respectively. Conclusion: No significant differences in PK of CBZ was found when CBZ was administered alone or in combination with NFX (P> 0.05).
Authors and Affiliations
Issam Abushammala, Mai Ramadan, Faten Abumhad
Keywords
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