The effect of tolterodine on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive containing ethinyl estradiol and levonorgestrel.
BACKGROUND
Tolterodine is an antimuscarinic agent for the treatment of overactive bladder, a chronic condition that is particularly common in women. Given the prevalence pattern of overactive bladder and the widespread use of oral contraception, circumstances are likely to arise in which physicians may wish to prescribe tolterodine for patients already taking oral contraceptives. Based on a search of MEDLINE from 1990 to 2001, there have been no studies of whether concomitant use of these agents entails a risk of drug-drug interaction or conception.


OBJECTIVE
This study investigated the effects of tolterodine on the pharmacokinetics and pharmacodynamics of a low-dose combination oral contraceptive (ethinyl estradiol 30 microg/levonorgestrel 150 microg).


METHODS
This was an open-label, randomized, 2-period crossover study in healthy women. Oral contraception was given for 21 days either alone or in combination with oral tolterodine 2 mg BID (on days 1-14) over two 28-day contraceptive cycles. Pharmacokinetic assessments were performed on day 14 based on plasma levels of ethinyl estradiol and levonorgestrel up to 24 hours after dosing and serum tolterodine levels at 1 to 3 hours after dosing. The potential for pharmacodynamic interaction was assessed in terms of the risk of failure of suppression of ovulation based on serum levels of estradiol and progesterone measured throughout each cycle.


RESULTS
Twenty-four healthy women (age, 23-41 years [mean, 30 years]; height, 155-178 cm [mean, 167 cm]; body weight, 51-75 kg [mean, 64 kg]) participated in the study. There was no evidence of a pharmacokinetic interaction between tolterodine and the steroid hormones in the oral contraceptive used, nor did the oral contraceptive show any relevant pharmacokinetic interaction with tolterodine. Serum levels of estradiol and progesterone indicated suppression of ovulation in both treatment periods.


CONCLUSIONS
In this selected population. coadministration of tolterodine did not affect the contraceptive efficacy of a low-dose combination oral contraceptive containing ethinyl estradiol and levonorgestrel.
Olsson
B
B
Experimental Medicine, Biovitrum AB, Stockholm, Sweden. Birgitta.Olsson@biovitrum.com
Landgren
B M
BM
D000328:Adult; D001559:Benzhydryl Compounds / Q000009:adverse effects* / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D003277:Contraceptives, Oral, Combined / Q000493:pharmacokinetics*; D003408:Cresols / Q000009:adverse effects* / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004958:Estradiol / Q000097:blood; D045166:Estradiol Congeners / Q000493:pharmacokinetics*; D004997:Ethinyl Estradiol / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000493:pharmacokinetics*; D018727:Muscarinic Antagonists / Q000009:adverse effects* / Q000378:metabolism*; D010060:Ovulation / Q000187:drug effects; D010665:Phenylpropanolamine; D011374:Progesterone / Q000097:blood; D045167:Progesterone Congeners / Q000493:pharmacokinetics*; D013997:Time Factors; D000068737:Tolterodine Tartrate
C109909:5-hydroxymethyl tolterodine; D001559:Benzhydryl Compounds; D003277:Contraceptives, Oral, Combined; D003408:Cresols; D045166:Estradiol Congeners; D018727:Muscarinic Antagonists; D045167:Progesterone Congeners; D010665:Phenylpropanolamine; D004997:Ethinyl Estradiol; D011374:Progesterone; D004958:Estradiol; D000068737:Tolterodine Tartrate; D016912:Levonorgestrel