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Effect of chronic oral contraceptive steroids on theophylline disposition

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Summary

The effect of chronic oral contraceptive (OC) usage on the disposition of theophylline was examined. Aminophylline solution (4 mg/kg) was given orally to 8 healthy female non-OC users and to 8 healthy women who were chronic (>6 months) OC users. The OC user group had a significantly lower total plasma clearance of theophylline than women not using OC (35.1±5.6 vs. 53.1±14.5 ml/h/kg). The t1/2 was also significantly prolonged in the OC group (9.79±1.43 vs. 7.34±1.75 h) while the volume of distribution was similar between the 2 groups. The serum ethinylestradiol (EE) concentrations after oral OC administration were measured simultaneously. The apparent clearance of EE was about 30% lower in the OC users. A significant positive correlation was found between the apparent clearance of EE and the plasma clearance of theophylline. The effects of OC are predominantly due to chronic use with decreased elimination of both theophylline and EE.

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References

  1. Breckenridge AM, Back DJ, Orme M (1979) Interactions between oral contraceptives and other drugs. Pharmacol Ther 7: 617–626

    Google Scholar 

  2. Bacon JF, Shenfield GM (1980) Pregnancy attributable to interaction between tetracycline and oral contraceptives. Br Med J 280: 293

    Google Scholar 

  3. Roberton YR, Johnson ES (1976) Interactions between oral contraceptives and other drugs: a review. Curr Med Res Opin 3: 647–661

    Google Scholar 

  4. Tephly TR, Mannering GJ (1968) Inhibition of drug metabolism. Mol Pharmacol 4: 10–14

    Google Scholar 

  5. Forker EL (1969) The effect of estrogen on bile formation in the rat. J Clin Invest 48: 654–663

    Google Scholar 

  6. Jusko WJ, Gardner MJ, Mangione A, Schentag JJ, Koup JR, Vance JW (1979) Factors affecting theophylline clearances: age, tobacco, marijuana, cirrhosis, congestive heart failure, obesity, oral contraceptives, benzodiazepines, barbiturates and ethanol. J Pharm Sci 68: 1358–1366

    Google Scholar 

  7. Miale JB, Kent JW (1974) Effects of oral contraceptives on results of laboratory tests. Am J Obstet Gynecol 120: 264–272

    Google Scholar 

  8. Ockner RK, Davidson CS (1967) Hepatic effects of oral contraceptives. N Engl J Med 276: 331–334

    Google Scholar 

  9. Jusko WJ, Poliszczuk A (1976) High pressure liquid chromatographic and spectrophotometric assays for theophylline in biological fluids. Am J Hosp Pharm 33: 1193–1196

    Google Scholar 

  10. Cook CE, Talbert CR, Christensen HD (1974) Antigens from synthetic and natural estrogens: formation by conjugation with protein through a thiopropionic acid link. Life Sci 14: 1075–87

    Google Scholar 

  11. de la Pena A, Chenault CB, Goldzieher JW (1975) Radioimmunoassay of unconjugated plasma ethynylestradiol in women. Steroids 25: 773–780

    Google Scholar 

  12. Goldzieher JW, Dozier TS, de la Pena A (1980) Plasma levels and pharmacokinetics of ethynyl estrogens in various populations. Contraception 21: 1–16

    Google Scholar 

  13. Yeh KC, Kwan KC (1978) Comparison of numerical integrating algorithms by trapezoidal, Lagrange, and spline approximation. J Pharmacokinet Biopharm 6: 79–98

    Google Scholar 

  14. Riggs DS, Guarnieri JA, Addelman S (1978) Fitting straight lines when both variables are subject to error. Life Sci 22: 1305–1360

    Google Scholar 

  15. Hendeles L, Weinberger M, Bighley L (1977) Absolute bioavailability of oral theophylline. Am J Hosp Pharm 34: 525–527

    Google Scholar 

  16. Brodie BB, Axelrod J, and Reichenthal J (1952) Metabolism of theophylline (1,3-dimethylxanthine) in man. J Biol Chem 194: 215–222

    Google Scholar 

  17. Weinberger M, Ginchansky E (1977) Dose-dependent kinetics of theophylline dispoition in asthmatic children. J Pediatr 91: 820–824

    Google Scholar 

  18. Abernethy DR, Greenblatt DJ (1981) Impairment of antipyrine metabolism by low dose oral contraceptive steroids. Clin Pharmacol Ther 29: 106–110

    Google Scholar 

  19. Carter DE, Goldman JM, Bressler R, Huxtable RJ, Christian CD, Heine MW (1974) Effect of oral contraceptives on drug metabolism. Clin Pharmacol Ther 15: 22–31

    Google Scholar 

  20. Herz R, Koelz HR, Haemmerli UP, Benes I, Blum AI (1978) Inhibition of hepatic demethylation of aminopyrine by oral contraceptive steroids in humans. Eur J Clin Invest 8: 27–30

    Google Scholar 

  21. Helton ED, Goldzieher JW (1977) The pharmacokinetics of ethynyl estrogens, a review. Contraception 15: 255–284

    Google Scholar 

  22. Levy G, Koysooko R (1976) Renal clearance of theophylline in man. J Clin Pharmacol 16: 329–332

    Google Scholar 

  23. Roberts RK, Desmond PV, Wilkinson GR, Schenker S (1979) Disposition of chlordiazepoxide: sex differences and effects of oral contraceptives. Clin Pharmacol Ther 25: 826–831

    Google Scholar 

  24. Homeida M, Halliwell M, Branch RA (1978) Effects of an oral contraceptive on hepatic size and antipyrine metabolism in premenopausal women. Clin Pharmacol Ther 24: 228–232

    Google Scholar 

  25. O'Malley K, Stevenson IH, Crooks J (1972) Impairment of human drug metabolism by oral contraceptive steroids. Clin Pharmacol Ther 13: 552–557

    Google Scholar 

  26. Field B, Lu C, Hepner GW (1979) Inhibition of hepatic drug metabolism by norethindrone. Clin Pharmacol Ther 25: 196–198

    Google Scholar 

  27. Patwardhan RV, Desmond PV, Johnson RF, Schenker S (1980) Impaired elimination of caffeine by oral contraceptive steroids. J Lab Clin Med 95: 603–608

    Google Scholar 

  28. Lohmann SM, Miech RP (1976) Theophylline metabolism by rat liver microsomal system. J Pharmacol Exp Ther 196: 213–225

    Google Scholar 

  29. Hunt SN, Jusko WJ, Yurchak AM (1976) Effect of smoking on theophylline disposition. Clin Pharmacol Ther 19: 546–551

    Google Scholar 

  30. Jusko WJ, Schentag JJ, Clark JH, Gardner M, Yurchak AM (1978) Enhanced biotransformation of theophylline in marihuana and tobacco smokers. Clin Pharmacol Ther 24: 406–410

    Google Scholar 

  31. Landay RA, Gonzalez MA, Taylor JC (1978) Effect of phenobarbital on theophylline disposition. J Allergy Clin Immunol 62: 27–29

    Google Scholar 

  32. MacKinnon M, Sutherland E, Simon FR (1977) Effects of ethinyl estradiol on hepatic microsomal proteins and the turnover of cytochrome P-450. J Lab Clin Med 90: 1096–1106

    Google Scholar 

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Tornatore, K.M., Kanarkowski, R., McCarthy, T.L. et al. Effect of chronic oral contraceptive steroids on theophylline disposition. Eur J Clin Pharmacol 23, 129–134 (1982). https://doi.org/10.1007/BF00545966

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  • DOI: https://doi.org/10.1007/BF00545966

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