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An interaction study between the new antiepileptic and CNS drug carisbamate (RWJ-333369) and lamotrigine and valproic acid.
Chien, Shuchean; Yao, Caiping; Mertens, Annemie; Verhaeghe, Tom; Solanki, Bhavna; Doose, Dennis R; Novak, Gerald; Bialer, Meir.
Afiliación
  • Chien S; Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan and Titusville, NJ, USA.
Epilepsia ; 48(7): 1328-38, 2007 Jul.
Article en En | MEDLINE | ID: mdl-17381436
PURPOSE: To characterize possible pharmacokinetic interactions between the new antiepileptic drug carisbamate (RWJ-333369) and valproic acid (VPA) or lamotrigine (LTG) following multiple dosing in healthy subjects. METHODS: Two open-label, sequential-design studies were conducted in 24 healthy adults. In Study 1, subjects received carisbamate alone (5 days 250 mg q12h; 5 days 500 mg q12h), then VPA alone (7 days 300 mg q12h; 7 days 500 mg q12h), and then a combination of VPA (500 mg q12h) and carisbamate (5 days 250 mg q12h; 5 days 500 mg q12h). In Study 2, subjects received carisbamate alone as in Study 1, then LTG alone (14 days 25 mg q12h; 14 days 50 mg q12h), and then combination of LTG (50 mg q12h) and carisbamate (3 days 250 mg q12h; 14 days 500 mg q12h). RESULTS: Coadministration of VPA or LTG had minimal effect on carisbamate mean C(max) and AUC(ss) values. Mean VPA-C(max) and AUC(ss) values were approximately 15% lower when given concomitantly with carisbamate. However, the 90% confidence intervals (CIs) for the C(max) and AUC(ss) ratio with/without carisbamate were within the 80-125% equivalence range, C(max) 82-89%; AUC(ss) 81-88%. Mean LTG C(max) and AUC(ss) values were approximately 20% lower when given concomitantly with carisbamate. The 90% CIs with and without carisbamate for LTG C(max) and AUC(ss) were 79-86% and 75-81%, respectively. This modest change is not considered clinically significant. CONCLUSIONS: There were no clinically significant interactions between carisbamate and VPA or LTG. Concomitant administration of carisbamate with VPA or LTG was generally safe and well tolerated.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Triazinas / Carbamatos / Ácido Valproico / Anticonvulsivantes Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Epilepsia Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Triazinas / Carbamatos / Ácido Valproico / Anticonvulsivantes Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Epilepsia Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos