Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1994 Oct;38(4):376–380. doi: 10.1111/j.1365-2125.1994.tb04370.x

Lansoprazole does not affect the bioavailability of oral contraceptives.

W Fuchs 1, R Sennewald 1, U Klotz 1
PMCID: PMC1364784  PMID: 7833230

Abstract

The effects of the proton pump inhibitor lansoprazole on the bioavailability of a low-dose oral contraceptive (OC), containing 0.03 mg ethinyloestradiol (EE) and 0.15 mg levonorgestrel (LNG), were investigated. Twenty-four healthy females (aged 19-35 years; weight 60.6 +/- 7.1 kg) participated in a multiple-dose, placebo-controlled, randomized two-way cross-over study. All subjects received the OC over 2 full menstrual cycles from day 1 to day 21 separated by a drug-free interval of 7 days. Lansoprazole (60 mg day-1) or placebo was coadministered for 3 weeks each. Plasma concentrations of EE and LNG were determined by GC-MS. The 90% confidence intervals for ratios of Cmax and AUC after log transformation of both EE and LNG ranged between 91 and 111%, indicating that lansoprazole did not affect the bioavailability of EE and LNG.

Full text

PDF
376

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersson T., Andrén K., Cederberg C., Edvardsson G., Heggelund A., Lundborg P. Effect of omeprazole and cimetidine on plasma diazepam levels. Eur J Clin Pharmacol. 1990;39(1):51–54. doi: 10.1007/BF02657057. [DOI] [PubMed] [Google Scholar]
  2. Andersson T., Lagerström P. O., Unge P. A study of the interaction between omeprazole and phenytoin in epileptic patients. Ther Drug Monit. 1990 Jul;12(4):329–333. doi: 10.1097/00007691-199007000-00005. [DOI] [PubMed] [Google Scholar]
  3. Andersson T. Omeprazole drug interaction studies. Clin Pharmacokinet. 1991 Sep;21(3):195–212. doi: 10.2165/00003088-199121030-00004. [DOI] [PubMed] [Google Scholar]
  4. Bachmann K. A., Sullivan T. J., Jauregui L., Reese J. H., Miller K., Levine L. Absence of an inhibitory effect of omeprazole and nizatidine on phenytoin disposition, a marker of CYP2C activity. Br J Clin Pharmacol. 1993 Oct;36(4):380–382. doi: 10.1111/j.1365-2125.1993.tb00382.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brody S. A., Turkes A., Goldzieher J. W. Pharmacokinetics of three bioequivalent norethindrone/mestranol-50 micrograms and three norethindrone/ethinyl estradiol-35 micrograms OC formulations: are "low-dose" pills really lower? Contraception. 1989 Sep;40(3):269–284. doi: 10.1016/0010-7824(89)90092-9. [DOI] [PubMed] [Google Scholar]
  6. Diaz D., Fabre I., Daujat M., Saint Aubert B., Bories P., Michel H., Maurel P. Omeprazole is an aryl hydrocarbon-like inducer of human hepatic cytochrome P450. Gastroenterology. 1990 Sep;99(3):737–747. doi: 10.1016/0016-5085(90)90963-2. [DOI] [PubMed] [Google Scholar]
  7. Dowie L. J., Smith J. E., MacGilchrist A. J., Fraser R., Honour J. W., Reid J. L., Kenyon C. J. In vivo and in vitro studies of the site of inhibitory action of omeprazole on adrenocortical steroidogenesis. Eur J Clin Pharmacol. 1988;35(6):625–629. doi: 10.1007/BF00637598. [DOI] [PubMed] [Google Scholar]
  8. Galbraith R. A., Michnovicz J. J. Omeprazole fails to alter the cytochrome P450-dependent 2-hydroxylation of estradiol in male volunteers. Pharmacology. 1993 Jul;47(1):8–12. doi: 10.1159/000139072. [DOI] [PubMed] [Google Scholar]
  9. Gugler R., Jensen J. C. Drugs other than H2-receptor antagonists as clinically important inhibitors of drug metabolism in vivo. Pharmacol Ther. 1987;33(1):133–137. doi: 10.1016/0163-7258(87)90041-6. [DOI] [PubMed] [Google Scholar]
  10. Gugler R., Jensen J. C. Omeprazole inhibits oxidative drug metabolism. Studies with diazepam and phenytoin in vivo and 7-ethoxycoumarin in vitro. Gastroenterology. 1985 Dec;89(6):1235–1241. [PubMed] [Google Scholar]
  11. Heinemeyer G., Roots I., Lestau P., Klaiber H. R., Dennhardt R. D-glucaric acid excretion in critical care patients--comparison with 6 beta-hydroxycortisol excretion and serum gamma-glutamyltranspeptidase activity and relation to multiple drug therapy. Br J Clin Pharmacol. 1986 Jan;21(1):9–18. doi: 10.1111/j.1365-2125.1986.tb02817.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Henry D. A., Somerville K. W., Kitchingman G., Langman M. J. Omeprazole: effects on oxidative drug metabolism. Br J Clin Pharmacol. 1984 Aug;18(2):195–200. doi: 10.1111/j.1365-2125.1984.tb02452.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jung-Hoffmann C., Kuhl H. Interaction with the pharmacokinetics of ethinylestradiol and progestogens contained in oral contraceptives. Contraception. 1989 Sep;40(3):299–312. doi: 10.1016/0010-7824(89)90094-2. [DOI] [PubMed] [Google Scholar]
  14. Key T. J., Pike M. C., Moore J. W., Bulbrook R. D., Clark G. M., Allen D. S., Wang D. Y. The relationships of SHBG with current and previous use of oral contraceptives and oestrogen replacement therapy. Contraception. 1989 Feb;39(2):179–186. doi: 10.1016/s0010-7824(89)80006-x. [DOI] [PubMed] [Google Scholar]
  15. Kuhl H., Jung-Hoffmann C., Heidt F. Serum levels of 3-keto-desogestrel and SHBG during 12 cycles of treatment with 30 micrograms ethinylestradiol and 150 micrograms desogestrel. Contraception. 1988 Sep;38(3):381–390. doi: 10.1016/0010-7824(88)90110-2. [DOI] [PubMed] [Google Scholar]
  16. Kuhnz W., Hümpel M., Schütt B., Louton T., Steinberg B., Gansau C. Relative bioavailability of ethinyl estradiol from two different oral contraceptive formulations after single oral administration to 18 women in an intraindividual cross-over design. Horm Res. 1990;33(1):40–44. doi: 10.1159/000181446. [DOI] [PubMed] [Google Scholar]
  17. Kuhnz W. Pharmacokinetics of the contraceptive steroids levonorgestrel and gestodene after single and multiple oral administration to women. Am J Obstet Gynecol. 1990 Dec;163(6 Pt 2):2120–2127. doi: 10.1016/0002-9378(90)90551-h. [DOI] [PubMed] [Google Scholar]
  18. Landes B. D., Miscoria G., Flouvat B. Determination of lansoprazole and its metabolites in plasma by high-performance liquid chromatography using a loop column. J Chromatogr. 1992 May 20;577(1):117–122. doi: 10.1016/0378-4347(92)80605-p. [DOI] [PubMed] [Google Scholar]
  19. Lefebvre R. A., Flouvat B., Karolac-Tamisier S., Moerman E., Van Ganse E. Influence of lansoprazole treatment on diazepam plasma concentrations. Clin Pharmacol Ther. 1992 Nov;52(5):458–463. doi: 10.1038/clpt.1992.172. [DOI] [PubMed] [Google Scholar]
  20. Lähteenmäki P., Nilsson C. G. Plasma concentrations of ethinylestradiol and D-norgestrel during two immediate postabortal oral contraceptive cycles. Contraception. 1978 Jan;17(1):9–17. doi: 10.1016/0010-7824(78)90055-0. [DOI] [PubMed] [Google Scholar]
  21. Nilsson S., Nygren K. G. Ethinyl estradiol in peripheral plasma after oral administration of 30 microgram and 50 microgram to women. Contraception. 1978 Nov;18(5):469–475. doi: 10.1016/0010-7824(78)90031-8. [DOI] [PubMed] [Google Scholar]
  22. Ohnhaus E. E., Park B. K. Measurement of urinary 6-beta-hydroxycortisol excretion as an in vivo parameter in the clinical assessment of the microsomal enzyme-inducing capacity of antipyrine, phenobarbitone and rifampicin. Eur J Clin Pharmacol. 1979 Mar 26;15(2):139–145. doi: 10.1007/BF00609878. [DOI] [PubMed] [Google Scholar]
  23. Orme M. L., Back D. J., Breckenridge A. M. Clinical pharmacokinetics of oral contraceptive steroids. Clin Pharmacokinet. 1983 Mar-Apr;8(2):95–136. doi: 10.2165/00003088-198308020-00001. [DOI] [PubMed] [Google Scholar]
  24. Orme M., Back D. J., Ward S., Green S. The pharmacokinetics of ethynylestradiol in the presence and absence of gestodene and desogestrel. Contraception. 1991 Apr;43(4):305–316. doi: 10.1016/0010-7824(91)90069-r. [DOI] [PubMed] [Google Scholar]
  25. Osikowska-Evers B. A., Eichelbaum M. A sensitive capillary GC assay for the determination of sparteine oxidation products in microsomal fractions of human liver. Life Sci. 1986 May 12;38(19):1775–1782. doi: 10.1016/0024-3205(86)90128-1. [DOI] [PubMed] [Google Scholar]
  26. Park B. K. Assessment of urinary 6 beta-hydroxycortisol as an in vivo index of mixed-function oxygenase activity. Br J Clin Pharmacol. 1981 Aug;12(2):97–102. doi: 10.1111/j.1365-2125.1981.tb01186.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Parkinson A., Hurwitz A. Omeprazole and the induction of human cytochrome P-450: a response to concerns about potential adverse effects. Gastroenterology. 1991 Apr;100(4):1157–1164. doi: 10.1016/0016-5085(91)90317-e. [DOI] [PubMed] [Google Scholar]
  28. Prichard P. J., Walt R. P., Kitchingman G. K., Somerville K. W., Langman M. J., Williams J., Richens A. Oral phenytoin pharmacokinetics during omeprazole therapy. Br J Clin Pharmacol. 1987 Oct;24(4):543–545. doi: 10.1111/j.1365-2125.1987.tb03209.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Quattrochi L. C., Tukey R. H. Nuclear uptake of the Ah (dioxin) receptor in response to omeprazole: transcriptional activation of the human CYP1A1 gene. Mol Pharmacol. 1993 Apr;43(4):504–508. [PubMed] [Google Scholar]
  30. Roots I., Holbe R., Hövermann W., Nigam S., Heinemeyer G., Hildebrandt A. G. Quantitative determination by HPLC of urinary 6beta-hydroxycortisol, an indicator of enzyme induction by rifampicin and antiepileptic drugs. Eur J Clin Pharmacol. 1979 Aug;16(1):63–71. doi: 10.1007/BF00644969. [DOI] [PubMed] [Google Scholar]
  31. Rost K. L., Brösicke H., Brockmöller J., Scheffler M., Helge H., Roots I. Increase of cytochrome P450IA2 activity by omeprazole: evidence by the 13C-[N-3-methyl]-caffeine breath test in poor and extensive metabolizers of S-mephenytoin. Clin Pharmacol Ther. 1992 Aug;52(2):170–180. doi: 10.1038/clpt.1992.126. [DOI] [PubMed] [Google Scholar]
  32. Stadel B. V., Sternthal P. M., Schlesselman J. J., Douglas M. B., Hall W. D., Kaul L., Ahluwalia B. Variation of ethinylestradiol blood levels among healthy women using oral contraceptives. Fertil Steril. 1980 Mar;33(3):257–260. doi: 10.1016/s0015-0282(16)44589-9. [DOI] [PubMed] [Google Scholar]
  33. Steinijans V. W., Hartmann M., Huber R., Radtke H. W. Lack of pharmacokinetic interaction as an equivalence problem. Int J Clin Pharmacol Ther Toxicol. 1991 Aug;29(8):323–328. [PubMed] [Google Scholar]
  34. Steinijans V. W., Hauschke D., Jonkman J. H. Controversies in bioequivalence studies. Clin Pharmacokinet. 1992 Apr;22(4):247–253. doi: 10.2165/00003088-199222040-00001. [DOI] [PubMed] [Google Scholar]
  35. Sutfin T., Balmer K., Boström H., Eriksson S., Höglund P., Paulsen O. Stereoselective interaction of omeprazole with warfarin in healthy men. Ther Drug Monit. 1989;11(2):176–184. doi: 10.1097/00007691-198903000-00010. [DOI] [PubMed] [Google Scholar]
  36. Tucker G. T. The interaction of proton pump inhibitors with cytochromes P450. Aliment Pharmacol Ther. 1994;8 (Suppl 1):33–38. doi: 10.1111/j.1365-2036.1994.tb00233.x. [DOI] [PubMed] [Google Scholar]
  37. Wedlund P. J., Sweetman B. J., McAllister C. B., Branch R. A., Wilkinson G. R. Direct enantiomeric resolution of mephenytoin and its N-demethylated metabolite in plasma and blood using chiral capillary gas chromatography. J Chromatogr. 1984 Apr 13;307(1):121–127. doi: 10.1016/s0378-4347(00)84078-5. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES