Nafimidone is a new antiepileptic drug which may be effective in partial onset seizures. We studied the pharmacokinetics of nafimidone and its metabolite, nafimidone alcohol, in 12 patients already taking phenytoin and/or carbamazepine. The half-life of nafimidone was 1.34 ± 0.48 hours after a 100mg single dose and 1.69 ± 0.91 hours after a 300mg single dose. However, the half-life of nafimidone alcohol increased from 2.84 ± 0.72 hours after a 100mg single dose to 4.22 ± 1.09 hours after a 300mg single dose (p < 0.02). The clearance of nafimidone was 43.56 ± 22.11 L/h/kg after a 100mg single dose and 35.51 ± 28.93 L/h/kg after the 300mg single dose. The respective apparent volumes of distribution of nafimidone after single 100 and 300mg doses were 80.78 ± 46.11 L/kg and 71.01 ± 36.86 L/kg. After short term (9 to 10 weeks) and long term (127 to 152 weeks) maintenance therapy on nafimidone 600mg per day the half-life of nafimidone alcohol was 2.23 ± 0.36 hours and 2.16 ± 0.60 hours, respectively. No nafimidone could be detected in urine but from 4 to 7% of the daily nafimidone dose was recovered as nafimidone alcohol. Thus, it appears that over 90% of the administered dose of nafimidone is metabolised by pathways other than glucuronidation of nafimidone alcohol and urinary excretion.