Effect of an oral contraceptive on the plasma levels of budesonide and prednisolone and the influence on plasma cortisol.
OBJECTIVE
To investigate whether the use of an oral contraceptive would influence plasma levels of budesonide (Entocort capsules) or prednisolone (plain tablets) during repeated oral administration of these glucocorticosteroids. Plasma concentrations of cortisol and ethinyl estradiol (INN, ethinylestradiol) were also compared.


METHODS
Forty healthy women took part in this single-blind, randomized placebo-controlled study with two parallel groups, where a three-way crossover design was applied within groups. One group was taking an oral contraceptive (150 microg desogestrel and 30 microg ethinyl estradiol); the other group (control) was not. On seven consecutive mornings, oral doses of 4.5 mg budesonide, 20 mg prednisolone, or placebo were administered. There was a washout period of at least one menstrual cycle between administration periods.


RESULTS
In the oral contraceptive users, the average plasma concentration of prednisolone was 131% higher than in the control group (P < .001), whereas the average plasma concentration of budesonide was only 22% higher (not significant). Mean plasma cortisol levels were suppressed by 90% and 82% with prednisolone and by 22% and 28% with budesonide in oral contraceptive users and the control subjects, respectively. The group difference was significant with prednisolone (P < .001) but not with budesonide. Ethinyl estradiol levels in plasma were not affected by administration of either glucocorticosteroid.


CONCLUSIONS
No difference was found in plasma levels of budesonide or in cortisol suppression after administration of budesonide capsules in women taking the oral contraceptive and those who were not. The oral contraceptive users had much higher plasma levels of prednisolone and greater cortisol suppression. This result suggests that oral budesonide can be used with maintained safety in women using oral contraceptives.
Seidegård
J
J
Experimental Medicine, AstraZeneca R&D Lund, Sweden.
Simonsson
M
M
Edsbäcker
S
S
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D019819:Budesonide / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology*; D018592:Cross-Over Studies; D017135:Desogestrel / Q000494:pharmacology; D004347:Drug Interactions; D045166:Estradiol Congeners / Q000097:blood; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D011239:Prednisolone / Q000097:blood* / Q000493:pharmacokinetics; D016037:Single-Blind Method
D003280:Contraceptives, Oral, Synthetic; D045166:Estradiol Congeners; D005938:Glucocorticoids; D004997:Ethinyl Estradiol; D019819:Budesonide; D017135:Desogestrel; D011239:Prednisolone; D006854:Hydrocortisone