Inhibition and induction of drug metabolism by psoralens: Alterations in duration of sleep induced by hexobarbital and in clearance of caffeine and hexobarbital in mice

Abstract

1. Hexobarbital (100 mg/kg i.p.) sleeping times in male CD-1 mice pretreated (-1 h) with a single i.p. injection of 150 μmol/kg of psoralen or coumarin analogues were increased, most markedly (6-fold) by linear, methoxy-substituted psoralens.

2. Hexobarbital sleeping times of mice which received three daily injections (231 μmol/kg; 50 mg/kg) of 8-methoxypsoralen (8-MOP) were 44% of controls (corn oil).

3. The whole-body half-life of caffeine (1 mg) in mice was 10˙2, 1˙2, and 0˙37 h following 8-MOP (50 mg/kg per day) × 1, vehicle, and 8-MOP × 3 respectively.

4. The whole-body concentrations of hexobarbital (100 mg/kg dose) in mice 30 min after dosing were 14˙3±0˙9, 8˙4±0˙3, and 5˙2±0˙5 μg/ml (1 mcuse = 150 ml) following 8-MOP (50 mg/kg per day) × 1, vehicle, and 8-MOP × 3 respectively.

5. It is concluded that, administered acutely, psoralen analogues inhibit hexobarbital metabolism in mice; and 8-MOP administered acutely inhibits the metabolism of caffeine and hexobarbital, but administered repeatedly increases their metabolism.