Flutoprazepam(KB-509)の生体内動態(第4報)イヌにおけるFlutoprazepam-2-¹⁴CおよびDesalkylflutoprazepam-2-¹⁴Cの血漿中動態

抄録

The pharmacokinetics of flutoprazepam (FP) and its major metabolite, desalkylflutoprazepam (DFP), was studied in dogs. Two tenth mg/kg flutoprazepam-2-¹⁴C were administered intravenously and oraly, and 0.2 mg/kg desalkylflutoprazepam-2-¹⁴C were administered intravenously to each of three dogs, respectively. The plasma levels of FP or DFP after bolus intravenous injection declined biexponentially and the hybrid pharmacokinetic parameters were estimated as follows (value for parameter±standard error) : A=111.4±43.4 ng/ml, B=21.9±7.3 ng/ml, α=0.0522±0.255 min^-1, β=0.00507±0.00116 min^-1 for FP ; A=109.2±44.9 ng/ml, B=121.7±38.5 ng/ml, α=0.0455±0.0374 min^-1, β=0.00999±0.00139 min^-1 for DFP. The first order absorption with a rate constant of 0.069 min^-1 was recognized by an application of the Loo-Riegelman method to FP plasma level vs. time data after oral administration. The time course of plasma levels of the active metabolite, DFP, after oral and intravenous administration of FP exhibited in parallel with those of intact drug in terminal phase. The apparent elimination of DFP in the terminal phase could be regarded as being reflected by that of FP, since the inherent β-value for DFP was larger than that for FP. Therefore, it suggests that an administration of FP may prolong the pharmacological efficacies.