Rilmazafone Hydrochloriode (RZ), a prodrug of benzodiazepine derivatives, is used clinically as a sleep inducer.
The pharmacokinetics of RZ in patients were studied to determine the clinical dose for patients with chronic renal failure.
Five patients (2 male, 3 female, aged 44-62yr) who participated in this study were undergoing hemodialysis. They were given RZ (1mg, p. o.) one time on the day of dialysis, and 5-7 days later on the day of non-dialysis. Blood samples were collected for 48hr after each administration to determine the concentrations of metabolites of RZ (M1, M2, MA, M3, M4). Pharmacokinetic profiles of RZ in these patients were compared with those in healthy volunteers (2mg, p. o.). Despite the dose difference and body weight difference (patients, 53kg (mean), volunteers, 60kg), Cmax's of M1 and M4 in patients were double and AUC's were five times those in healthy volunteers. T1/2's of M1, M2, M4 in patients were two to four times longer than those in healthy volunteers. The pharmacokinetic profiles of total active metabolites in patients were not significantly different. However, plasma concentration-time curves of potent active metabolites (M1, M2) in patients would probably be higher than those in healthy volunteers, if both were given the same dose of RZ.
These results may indicate that dosage of RZ in patients with chronic renal failure should be started from 1mg, because of the reduction of hepatic metabolism and renal excretion of RZ in these patients.
