title: Pharmacokinetic interaction between albendazole sulfoxide enantiomers and antiepileptic drugs in patients with neurocysticercosis.
abstract: The aim of the present investigation was to determine the interaction between the antiepileptic drugs (AEDs) phenytoin, carbamazepine, and phenobarbital and the enantioselective metabolism of albendazole. Thirty-two adults with a diagnosis of the active form of intraparenchymatous neurocysticercosis and treated with albendazole at the dose of 7.5 mg/kg every 12 hours for 8 days were studied. The patients were divided into four groups based on the combined use of AEDs or not: control group (n = 9), phenytoin group (n = 9 patients treated with 3-4 mg/kg/d sodium phenytoin), carbamazepine group (n = 9 patients treated with 10-20 mg/kg/d carbamazepine), and phenobarbital group (n = 5 patients treated with 1.5-4.5 mg/kg/d phenobarbital). Serial blood collections were carried out on day 8 of albendazole treatment during the last 12-hour dose interval. Plasma concentrations of the (+)- and (-)-albendazole sulfoxide (ASOX) and albendazole sulfone (ASON) metabolites were determined by high-performance liquid chromatography using a chiral phase column and fluorescence detection. The pharmacokinetic parameters were analyzed by analysis of variance followed by the Tukey-Kramer test. The results are reported as means. The following differences (P < 0.05) were observed between the control and the phenytoin, carbamazepine, and phenobarbital groups, respectively: (+)-ASOX area under the concentration-time curve for 0 to 12 hours after treatment (AUC(0-12)) 6.1, 2.1, 3.1, 2.4 microg/h/mL; (+)-ASOX maximum plasma concentration (C(max)) 0.8, 0.3, 0.4, 0.3 microg/mL; (+)-ASOX half-life (t1/2) 8.0, 3.8, 4.1, 4.9 h; (-)-ASOX AUC(0-12) 1.8, 0.4, 0.6, 0.5 microg/h/mL; (-)-ASOX C(max) 0.2, 0.06, 0.1, 0.1 microg/mL; (-)-ASOX (t(1/2)) 4.3, 1.9, 2.2, 2.1 h; ASON AUC(0-12) 0.5, 0.2 microg/h/mL; ASON C(max) 0.8, 0.3, 0.4, 0.3 microg/mL; ASON (t(1/2)) 8.0, 3.8, 4.1 h. The results show that phenytoin, carbamazepine, and phenobarbital induce to approximately the same extent the oxidative metabolism of albendazole in a nonenantioselective manner. Notably, a significant reduction in the plasma concentration of the active ASOX metabolite was observed in patients with neurocysticercosis treated with these AEDs.
authors.affiliation: Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Vera L
authors.initials: VL
authors.lastname: Lanchote
authors.forename: Fabíola S
authors.initials: FS
authors.lastname: Garcia
authors.forename: Sônia A C
authors.initials: SA
authors.lastname: Dreossi
authors.forename: Osvaldo Massaiti
authors.initials: OM
authors.lastname: Takayanagui
mesh_terms: D000328:Adult; D015766:Albendazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000871:Anthelmintics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D002220:Carbamazepine / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007536:Isomerism; D008297:Male; D020019:Neurocysticercosis / Q000188:drug therapy; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology
chemical_list: D000871:Anthelmintics; D000927:Anticonvulsants; D002220:Carbamazepine; D010672:Phenytoin; D015766:Albendazole; C027186:albendazole sulfoxide; D010634:Phenobarbital