OBJECTIVES: The influence of the new antiepileptic drug losigamone (CAS 
112856-44-7/123783-52-8) on the pharmacokinetics of a combined oral 
contraceptive containing ethinylestradiol (CAS 57-63-6) and levonorgestrel (CAS 
797-63-7) was investigated in 16 healthy women.
METHODS: This phase I study consisted of 3 periods with an uncontrolled first 
period and a double-blind, placebo-controlled, cross-over design in the second 
and third period. All subjects received a single dose of 200 mg losigamone (1 
tablet) in period 1 (on day 14) as well as multiple doses of losigamone (3 
tablets = 600 mg per day) or placebo for 15 days in periods 2 and 3. During all 
three periods an oral contraceptive containing 30 microg ethinylestradiol and 
150 microg levonorgestrel was given. Single-dose pharmacokinetics was 
investigated on day 14 of period 1. Multiple-dose pharmacokinetic investigations 
were performed on day 15 of periods 2 and 3. The samples were assayed to derive 
pharmacokinetic data of ethinylestradiol and levonorgestrel. In addition, the 
concentrations of losigamone racemate (AO-33) and its enantiomers AO-242 and 
AO-294 were determined in these samples.
RESULTS: The mean values of the pharmacokinetic parameters AUC and Cmax of 
ethinylestradiol and levonorgestrel after multiple-dose treatment with 
losigamone or placebo were quite similar and met the criteria for 
bioequivalence. The 90% confidence intervals of the log-transformed ratios of 
the geometric means of the primary pharmacokinetic variables were included in 
the respective acceptance ranges of 80% to 125% (AUC) and 70% to 143% (Cmax).
CONCLUSIONS: The study demonstrated that multiple doses of losigamone did not 
influence the multiple dose kinetics of ethinylestradiol and levonorgestrel. The 
single- and multiple-dose kinetics of 200 mg losigamone and its enantiomeres did 
not differ from each other in a significant way. The combination of losigamone 
and the combined oral contraceptive was well tolerated and no serious adverse 
events occurred. It can be stated that the antiepileptic drug losigamone and the 
combined contraceptive do not interact each others metabolism.