An Interaction Study Between the New Antiepileptic and CNS Drug Carisbamate (RWJ‐333369) and Lamotrigine and Valproic Acid

Summary:  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 ∼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 ∼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.