1 The present study was designed to investigate both pharmacodynamic and pharmacokinetic interactions of clobazam and alcohol.
2 Eight healthy male volunteers participated in an intraindividual Latin square comparison of (a) clobazam 20 mg; (b) placebo; (c) alcohol + placebo; and (d) alcohol + clobazam 20 mg. Alcohol was administered orally in quantities individually calculated to yield serum alcohol concentrations of about 1000 μg/ml. The comparison of treatments (a) against (b) against (b) and (c) against (d) was double blind. Drug-free periods between the trials were 7 days.
3 Pharmacodynamic assessments were carried out before and 2, 3 and 5 h after administration using a series of tests of choice reaction performance, simple reaction time, two-hand coordination and body sway, together with self ratings, side-effects lists, vital signs and blood chemistry.
4 Blood samples were obtained before and 50, 100, 160, 220, 280, 340 and 1440 min after administration. Serum levels of clobazam and alcohol were determined by gas chromatography.
5 The dynamic results show significant differences between the alcohol and non-alcohol treatments and no significant difference either between clobazam and placebo, or between alcohol alone and alcohol + clobazam. Numerically, however, the detrimental effects of the combination were consistently stronger, indicating a possible pharmacodynamic interaction.
6 A pharmacokinetic interaction was found, as the serum clobazam levels were higher after combined administration of clobazam and alcohol than after clobazam alone. An enhanced absorption of clobazam and a reduced distribution volume may explain this finding which is comparable to findings obtained with diazepam and alcohol (Hayes et al., 1977).
7 It is concluded that combined ingestion of clobazam and alcohol is likely to be more hazardous than that of alcohol alone.