No pharmacokinetic interaction between lacosamide and carbamazepine in healthy volunteers.
Lacosamide is a new antiepileptic drug for adjunctive treatment of adult partial-onset seizures. Two open-label, multiple-dose clinical trials were conducted to evaluate the potential for pharmacokinetic interaction between lacosamide and carbamazepine. The influence of carbamazepine on lacosamide pharmacokinetics (trial A) and lacosamide on carbamazepine pharmacokinetics (trial B) was investigated in 19 (trial A) and 18 (trial B) healthy male participants. Trial A participants received lacosamide 200 mg bid alone and with carbamazepine 200 mg bid. Trial B participants received carbamazepine 200 mg bid alone and with lacosamide 200 mg bid. Pharmacokinetic parameters, area under the concentration-time curve during a dosage interval at steady state (AUC(tau,ss)), and maximum steady-state plasma drug concentration during a dosage interval (C(max,ss)) of lacosamide, carbamazepine, and carbamazepine-10,11-epoxide were measured and compared for each drug alone and together. The AUC(tau,ss) and C(max,ss) point estimates (combined vs sole treatment) showed relative bioavailability of approximately 100% for both drugs. All 90% confidence intervals of AUC(tau,ss) and C(max,ss) were within the generally accepted bioequivalence ranges of 80% to 125%. No changes in rate or extent of absorption or terminal half-life were observed. These results suggest that lacosamide and carbamazepine have a low potential for pharmacokinetic drug-drug interaction in clinical use.
Cawello
Willi
W
SCHWARZ BIOSCIENCES GmbH, A Member of the UCB Group, Global Exploratory Development, Pharmacometrics, Alfred-Nobel-Strasse 10, D-40789 Monheim, Germany. Willi.Cawello@ucb.com
Nickel
Brunhild
B
Eggert-Formella
Andrea
A
D000081:Acetamides / Q000097:blood / Q000493:pharmacokinetics*; D000293:Adolescent; D000328:Adult; D002220:Carbamazepine / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions / Q000502:physiology; D006801:Humans; D000078334:Lacosamide; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D000081:Acetamides; D002220:Carbamazepine; D000078334:Lacosamide