アドレナリンβ-遮断薬o-[3-(tert-Butylamino)-2-hydroxypropoxy]benzonitrile(Bunitrolol)の代謝に及ぼす投与経路の影響

抄録

The metabolic fate of o-[3-(tert-butylamino)-2-hydroxypropoxyl] benzonitrile (Bunitrolol) in the rat was studied by using the drug labeled with ¹⁴C in the nitrile group. Urine samples collected for 24 hr after oral or intravenous administration contained about 60% of the dosed ¹⁴C. The amount of unchanged Bunitrolol in urine was small after both routes of administration. The major metabolite was conjugated 4-hydroxybunitrolol, which constituted about 90% of the urinary ¹⁴C after oral administration and about 70% after intravenous administration. The amount of free 4-hydroxybunitrolol was relatively small. The sum of the recovery of 4-hydroxybunitrolol and conjugated 4-hydroxybunitrolol was almost equal after both routes of administration. Two minor metabolites were detected. One of them was conjugated 2-hydroxybenzonitrile and the other was probably 3-(2-cyanophenoxy)-2-hydroxypropionic acid. Most of the metabolites in bile was conjugated 4-hydroxybunitrolol. Blood concentration of free 4-hydroxybunitrolol in the postdistributive phase was about 25-33% of the corresponding values of the parent drug after oral administration and about 5-9% after intravenous administration. These findings were different from the fact that 4-hydroxypropranolol was detected in the systemic circulation after oral administration of propranolol but not after intravenous administration. This difference would be explained by the predominant biotransformation of bunitrolol to 4-hydroxybunitrolol.