A pharmacokinetic and pharmacodynamic study of flunitrazepam

Flunitrazepam was given as an induction agent i.v. to 12 patients undergoing otologic operations. Pharmacokinetics were evaluated from serum samples at 5 min-72 h by 63Ni-EC-GLC. Pharmacodynamic characteristics were estimated subjectively by simple questionnaire and objectively by the anesthetist during and after anesthesia. The dose of flunitrazepam required for anesthesia varied from 14 to 33 (mean 21) micrograms/kg and was not related to age. The mean distribution volumes of flunitrazepam, calculated by the three-compartment open model, were Vd1 0.61 (SD = 0.36) l/kg, Vd2 1.4 (SD = 0.70) l/kg, and Vd3 3.6 (SD = 1.39) l/kg. The mean elimination half-life was 25 h and serum clearance was 94 ml/min. The maximum decreases in blood pressure during anesthesia correlated with the age of the patients. The general assessment of the anesthetist about this form of anesthesia was positive in 75% of the 12 cases. A clear anterograde amnesia was found.