Ursodeoxycholic acid does not affect ethinylestradiol bioavailability in women taking oral contraceptives.
OBJECTIVE
Contraception is recommended for female patients during ursodeoxycholic acid (UDCA) treatment for the potential teratogenic effect of this bile acid, and the aim of our study was to determine whether this treatment affects the bioavailability of ethinylestradiol (EE2).


METHODS
In this double-blind, randomised study, we measured EE2 pharmacokinetics in eight healthy volunteers randomly allocated to receive oral contraceptive (30 microg EE2 and 75 microg gestodene) plus either UDCA (8-10 mg/kg per day) or placebo for 21 days during the first of three consecutive menstrual cycles. After a washout period during the second cycle, the subjects received the alternative treatment during the third menstrual cycle. Serum EE2 and UDCA were measured using radioimmunoassay and gas chromatography-mass spectrometry, respectively.


RESULTS
The profile for serum EE2 concentration was similar during UDCA (mean maximum serum concentration 177 pg/ml, SEM 59) and during placebo treatment (153 pg/ml, SEM 62), and mean area under the curve (AUC) was 1374 pg/h per ml (SEM 580) and 1320 pg/h per ml (SEM 551) during the two regimens, respectively. The point estimates and 90% confidence intervals of UDCA/placebo ratios for EE2 AUC and for maximum serum concentration were 1.1 (0.8-1.5) and 1.2 (1.0-1.4), respectively. Mean serum triglycerides concentration increased from 58.3 mg/dl (SEM 6.8) at enrolment to 91.4 mg/dl (SEM 10.7) during placebo (P < 0.01) and to 88.6 mg/dl (SEM 13.7) during UDCA treatment (P < 0.05). During UDCA treatment, serum enrichment with this bile acid and with the metabolite iso-UDCA was 29% (16%) and 3% (2%), respectively.


CONCLUSIONS
Co-administration with UDCA does not affect the bioavailability of EE2 in healthy volunteers, indicating that contraceptive efficacy is not affected.
Gastroenterology Unit, Medicine 1, University and Spedali Civili of Brescia, 25125 Brescia, Italy.
Ornella
O
Baisini
Federica
F
Benini
Felice
F
Petraglia
Wilhelm
W
Kuhnz
Santo
S
Scalia
Hanns-Ulrich
HU
Marschall
Gabriele
G
Brunetti
Horst-Dietmar
HD
Tauschel
Alberto
A
Lanzini
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002756:Cholagogues and Choleretics / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D003276:Contraceptives, Oral; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D004967:Estrogens / Q000097:blood / Q000493:pharmacokinetics*; D004997:Ethinyl Estradiol / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008597:Menstrual Cycle / Q000187:drug effects; D014280:Triglycerides / Q000097:blood; D014580:Ursodeoxycholic Acid / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*
D002756:Cholagogues and Choleretics; D003276:Contraceptives, Oral; D004967:Estrogens; D014280:Triglycerides; D004997:Ethinyl Estradiol; D014580:Ursodeoxycholic Acid; D002784:Cholesterol