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Abstract

EFFECT OF RIFAMPICIN ON PHARMACOKINETICS OF CARBAMAZEPINE IN RABBITS

*Issam Abushammala, Kamal Fakher Abu Shammaleh, Mohammed Taha 

ABSTRACT

Introduction: This study was conducted to investigate the effect of rifampicin (RIF) - a potent CYP3A inducer - on the pharmacokinetics (PK) of carbamazepine (CBZ) in healthy male rabbits. Methodology: Six rabbits were involved over two periods. In the first period each rabbit received a single oral dose of CBZ (40 mg/Kg). After a washout period of ten days the second period started by giving each rabbit oral dose of RIF (50 mg/Kg) for three consecutive days. On the fourth day RIF was given concurrently with CBZ in the same doses. Serial blood samples were collected after CBZ administration over 24 hours. Chemiluminescent enzyme immunoassay (CLEIA) was used to measure CBZ in serum. The PK of CBZ; Cmax, tmax, t 1/2, AUC0-t, AUC 0-∞, and ke were determined for the two periods using noncompartmental analysis. Results: Mean of pharmacokinetic parameters of CBZ administered alone (first period) or in combination (second period) were; Cmax, 9.17 ± 2.30 μg/mL versus 8.22 ± 6.68 μg/ml, tmax 2.08 ± 1.09 h versus 2.41 ± 0.97 h, AUC0-t 104.1 ± 25.5 μg·h/ml versus 92.0 ± 42.8 μg·h/ml, AUC0-∞ 189.3 ± 43.6 μg·h/ml versus 163.1 ± 54.1 μg·h/mL, t ½ 21.8 ± 3.28 h versus 22.89 ± 8.95 h and ke 0.0324 ± 0.005 h-1 versus 0.0348 ± 0.015 h-1, respectively. No statistical differences were found in the mean of PK of CBZ (P > 0.05) between two periods. Conclusion: In this study the effect of RIF on PK of CBZ was not established.

Keywords: Rifampicin, Pharmacokinetics, Carbamazepine, CYP3A4.


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