Kinetics of an orally absorbed aldose reductase inhibitor, sorbinil

Kinetics of sorbinil, an orally absorbed reductase inhibitor, were examined in man. Peak plasma concentrations were 0.95 micrograms/ml after a single 50-mg oral dose and 3.6 micrograms/ml after a 250-mg dose. The apparent volume of distribution was 840 ml/kg. Elimination from plasma was slow with a terminal half-life between 6 and 24 hr after dose of 34 to 52 hr and a renal clearance of 6.0 ml/min/1.73 m2. Administration of 50 mg/day for 5 days induced a mean peak serum concentration of 1.9 micrograms/ml. A dose of 250 mg/day for 10 days induced a peak serum concentration of 10.6 micrograms/ml. A mean of one-third of the dose was ultimately recovered unchanged in urine. Sorbinil kinetics make it suitable for once-a-day dosing.