抄録
We investigated the pharmacokinetic effects of nitrazepam (NZP, 5 mg), a benzodiazepinehypnotic, and rilmazafone hydrochloride (RMZ, 2 mg), a benzodiazepine prodrug with andwithout ethanol (0.7 g/kg body weight).
The study was carried out using the double-blind cross-over blockade design with placeboand vehicle. There were no significant differences in the pharmacokinetic parameters betweenhypnotics alone and hypnotics with ethanol, except for mean residence time (MRT) of RMZ . However, individual variations were found in the serum concentrations of the two hypnotic safter the ethanol consumption as indicated by pharmacokinetic parameters, Cmax and absorption rate. Furthermore, the AUC was lowered in NZP and increased in RMZ in 3 out of8 volunteers with ethanolcombined treatments . These findings were interpreted to reflect thedifferences in metabolic processes between NZP and RMZ; RMZ is metabolized throughdemethylation, while nitro-reduction is involved in the metabolism of NZP.
Regarding RMZ, the serum concentrations of the active metabolites, M-1, M-2, M-Aand M-3 were also measured in two volunteers. Ethanolcombined treatments caused a higherconcentration of M-1 in comparison with RMZ treatment alone. This might be due toblockade of the demethylation process from M-1 to M-2 by ethanol.
