Modified elimination of prednisolone in epileptic patients on carbamazepine monotherapy, and in women using low-dose oral contraceptives.
The pharmacokinetics of prednisolone in serum after prednisolone-21-phosphate intravenous infusion was compared in 8 chronic epileptic patients on carbamazepine monotherapy for 2 to 12 months, in 5 healthy females having used low-dose oral contraceptives (30-40 micrograms ethinylestradiol + 50-250 micrograms levonorgestrel) for 7 to 24 months, and in 9 other healthy subjects (5 females not using oral contraceptives, and 4 males). Elimination half-lives were shorter in the patients than in the 9 healthy subjects (1.98 +/- 0.48 versus 2.73 +/- 0.76 h, mean +/- SD, 0.02 less than p less than 0.05), and total clearances higher (4.20 +/- 0.53 versus 2.96 +/- 0.54 ml X min-1 X kg-1, p less than 0.02), while the volumes of distribution did not differ significantly. Among the healthy subjects, the oral contraceptive group exhibited a longer elimination half-life, and a lower total clearance, than each of the other two groups, who gave similar results (respectively 4.75 +/- 1.27, 3.05 +/- 0.75, and 2.33 +/- 0.66 h, p less than or equal to 0.05; 1.91 +/- 0.57, 2.95 +/- 0.60, and 2.97 +/- 0.57 ml X min-1 X kg-1, p less than or equal to 0.05); the volumes of distribution were not significantly different. These findings suggest that long-term treatments by carbamazepine and by these low-dose oral contraceptives may respectively increase and decrease the therapeutic requirements of prednisolone.
D000328:Adult; D002220:Carbamazepine / Q000627:therapeutic use*; D003278:Contraceptives, Oral, Hormonal / Q000494:pharmacology*; D004347:Drug Interactions; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D019304:Ethinyl Estradiol-Norgestrel Combination; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009644:Norgestrel / Q000494:pharmacology*; D011239:Prednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism*
D003278:Contraceptives, Oral, Hormonal; D002220:Carbamazepine; D009644:Norgestrel; D004997:Ethinyl Estradiol; C009022:prednisolone phosphate; D019304:Ethinyl Estradiol-Norgestrel Combination; D011239:Prednisolone