title: Kainic acid does not modify the oral pharmacokinetics of carbamazepine in rats.
abstract: Carbamazepine (CBZ) is a widely used antiepileptic agent that frequently interacts with other drugs. Recently, it has been reported that CBZ is able to modify the disturbed sleep patterns induced by kainic acid in epileptics. As a pharmacokinetic-pharmacodynamic characterization in the same animal is not possible due to the stress induced by blood sampling, it is important to establish if kainic acid is able to modify the pharmacokinetics of CBZ. Two groups of seven rats were used in this study. Animals received an oral dose of 50 mg/kg of CBZ alone or with 10 mg/kg of kainic acid. Blood samples (0.1 mL) were obtained at selected times for 12 hr and stored frozen until analyzed by HPLC. Pharmacokinetic parameters were: Cmax 6.51 +/- 1.32 and 6.63 +/- 0.95 microg/mL, tmax 3.55 +/- 0.98 and 1.82 +/- 0.59 hr, AUC 66.61 +/- 28.16 and 73.54 +/- 15.35 microg x h/mL and t1/2 7.16 +/- 2.55 and 5.80 +/- 1.37 hr. No statistically significant difference was observed in any parameter indicating that kainic acid is not able to modify oral pharmacokinetics of CBZ and pharmacokinetic-pharmacodynamic studies may be carried out using two groups of animals, one for the pharmacodynamics and another for the pharmacokinetic evaluation.
authors.affiliation: Torre de Investigación, Instituto Nacional de Pediatría, México.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pérez-Guillé
authors.forename: Miriam del Carmen
authors.initials: Mdel C
authors.lastname: Carrasco-Portugal
authors.forename: Alfonso
authors.initials: A
authors.lastname: Alfaro-Rodríguez
authors.forename: Norma
authors.initials: N
authors.lastname: Labra-Ruiz
authors.forename: Rosa
authors.initials: R
authors.lastname: Soriano-Rosales
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Flores-Murrieta
authors.forename: Fructuoso
authors.initials: F
authors.lastname: Ayala-Guerrero
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002220:Carbamazepine / Q000493:pharmacokinetics*; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D006207:Half-Life; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D002220:Carbamazepine; D007608:Kainic Acid