An interaction study between the New Antiepileptic and CNS drug carisbamate (RWJ-333369) and lamotrigine and valproic acid

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 I, 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 ql2h; 5 days 500 mg ql2h). In Study 2, subjects received carisbamate alone as in Study I, then LTG alone (14 days 25 mg q12h; 14 days 50 mg ql2h), and then combination of LTG (50 mg ql2h) and carisbamate (3 days 250 mg q12h; 14 days 500 mgq12h). Results: Coadministration of VPA or LTG had minimal effect and AUCss values were ∼ 15% lower when given concomitantly with carisbamate. However, the 90% confidence intervals (CIs) for the Cmax and AUCss ratio with/without carisbamate were within the 80-125% equivalence range, Cmax 82-89%; AUCss 81-88%. Mean LTG Cmax and AUCss values were ∼20% lower when given concomitantly with carisbamate. The 90% CIs with and without carisbamate for LTG Cmax and AUCss 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.