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.
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 mumol/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 mumol/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) x 1, vehicle, and 8-MOP x 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 micrograms/ml (1 mouse = 150 ml) following 8-MOP (50 mg/kg per day) x 1, vehicle, and 8-MOP x 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.
Apseloff
G
G
Department of Pharmacology, College of Medicine, Ohio State University, Columbus.
Hilliard
J B
JB
Gerber
N
N
Mays
D C
DC
D000818:Animals; D002110:Caffeine / Q000493:pharmacokinetics*; D003374:Coumarins / Q000494:pharmacology; D011564:Furocoumarins / Q000494:pharmacology*; D006207:Half-Life; D006591:Hexobarbital / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008730:Methoxsalen / Q000494:pharmacology; D051379:Mice; D012890:Sleep / Q000187:drug effects*; D013997:Time Factors; D014859:Warfarin / Q000494:pharmacology
D003374:Coumarins; D011564:Furocoumarins; D002110:Caffeine; D014859:Warfarin; D006591:Hexobarbital; D008730:Methoxsalen