Abstract
The dose dependency of carbamazepine pharmacokinetics was characterized in rats, a common test animal for antiepileptic drug efficacy. With a randomized Latin square schedule, 5, 10, and 20 mg/kg doses of carbamazepine were injected intravenously into six Sprague-Dawley rats followed by the administration of a 5 or 10 mg/kg i.v. dose of CBZ-E to each rat. Following administration, the concentrations of CBZ and Carbamazepine-10,11-epoxide (CBZ-E) in whole blood were determined by a reverse-phase HPLC assay. Plasma protein binding of both carbamazepine and CBZ-E was linear over the concentration range observed in this study. Carbamazepine concentration–time plots were log-linear, but the slopes were not parallel. Carbamazepine total-body clearances were 15.1 ± 3.26, 13.4 ± 5.66, and 10.0 ± 3.11 ml/min/kg at the 5, 10, and 20 mg/kg doses, respectively (significance of difference between the 5 and the 20 mg/kg dose = 0.06 < P < 0.05; Kruskal–Wallis test, Dunn's procedure). However, the formation clearance to CBZ-E did not change, suggesting that metabolism via other pathways was decreased at higher carbamazepine doses.
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Remmel, R.P., Sinz, M.W. & Cloyd, J.C. Dose-Dependent Pharmacokinetics of Carbamazepine in Rats: Determination of the Formation Clearance of Carbamazepine-10,11-epoxide. Pharm Res 7, 513–517 (1990). https://doi.org/10.1023/A:1015872901523
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DOI: https://doi.org/10.1023/A:1015872901523