title: An interaction study between the new antiepileptic and CNS drug carisbamate (RWJ-333369) and lamotrigine and valproic acid.
abstract: OBJECTIVE
  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.
authors: Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan and Titusville, NJ, USA.
authors: Shuchean
authors: S
authors: Chien
authors: Caiping
authors: C
authors: Yao
authors: Annemie
authors: A
authors: Mertens
authors: Tom
authors: T
authors: Verhaeghe
authors: Bhavna
authors: B
authors: Solanki
authors: Dennis R
authors: DR
authors: Doose
authors: Gerald
authors: G
authors: Novak
authors: Meir
authors: M
authors: Bialer
mesh_terms: D000927:Anticonvulsants / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002219:Carbamates / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D006801:Humans; D000077213:Lamotrigine; D014227:Triazines / Q000493:pharmacokinetics*; D014635:Valproic Acid / Q000493:pharmacokinetics*
chemical_list: D000927:Anticonvulsants; D002219:Carbamates; C518914:S-2-O-carbamoyl-1-o-chlorophenyl-ethanol; D014227:Triazines; D014635:Valproic Acid; D000077213:Lamotrigine