Evaluation of a pharmacokinetic interaction between remacemide hydrochloride and phenobarbitone in healthy males

Aims To determine whether there is pharmacokinetic interaction between the antiepileptic drugs remacemide and phenobarbitone. Methods In a group of 12 healthy adult male volunteers, the single dose and steady-state kinetics of remacemide were each determined twice, once in th e absence and once in the presence of phenobarbitone. The effect of 7 days remacemide intake on initial steady-state plasma phenobarbitone concentrati ons was also investigated. Results Apparent remacemide clearance (CL/F) and elimination half-life valu es were unchanged after 7 days intake of the drug in the absence of phenoba rbitone (1.25 +/- 0.32 vs 1.18 +/- 0.22 l kg(-1) h(-1) and 3.29 +/- 0.68 vs 3.62 +/- 0.85 h, respectively). Concomitant administration of remacemide w ith phenobarbitone resulted in an increase in the estimated CL/F of remacem ide (1.25 +/- 0.32 vs 2.09 +/- 0.53 l kg(-1) h(-1)) and a decreased remacem ide half-life (3.29 +/- 0.68 vs 2.69 +/- 0.33 h). The elimination of the de sglycinyl metabolite of remacemide also appeared to be increased after the phenobarbitone intake (half-life 14.72+/-2.82. vs 9.61+/-5.51 hh AUC 1532+/ -258 vs 533 +/- 281 ng ml(-1) h). Mean plasma phenobarbitone concentrations rose after 7 days of continuing remacemide intake (12.67 +/- 1.31 vs 13.86 +/- 1.81 mug ml(-1)). Conclusions Phenobarbitone induced the metabolism of remacemide and that of its desglycinyl metabolite. Remacemide did not induce its own metabolism, but had a modest inhibitory effect on the clearance. of phenobarbitone.