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
Breckenridge AM, Back DJ, Orme M (1979) Interactions between oral contraceptives and other drugs. Pharmacol Ther 7: 617–626
Bacon JF, Shenfield GM (1980) Pregnancy attributable to interaction between tetracycline and oral contraceptives. Br Med J 280: 293
Roberton YR, Johnson ES (1976) Interactions between oral contraceptives and other drugs: a review. Curr Med Res Opin 3: 647–661
Tephly TR, Mannering GJ (1968) Inhibition of drug metabolism. Mol Pharmacol 4: 10–14
Forker EL (1969) The effect of estrogen on bile formation in the rat. J Clin Invest 48: 654–663
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
Miale JB, Kent JW (1974) Effects of oral contraceptives on results of laboratory tests. Am J Obstet Gynecol 120: 264–272
Ockner RK, Davidson CS (1967) Hepatic effects of oral contraceptives. N Engl J Med 276: 331–334
Jusko WJ, Poliszczuk A (1976) High pressure liquid chromatographic and spectrophotometric assays for theophylline in biological fluids. Am J Hosp Pharm 33: 1193–1196
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
de la Pena A, Chenault CB, Goldzieher JW (1975) Radioimmunoassay of unconjugated plasma ethynylestradiol in women. Steroids 25: 773–780
Goldzieher JW, Dozier TS, de la Pena A (1980) Plasma levels and pharmacokinetics of ethynyl estrogens in various populations. Contraception 21: 1–16
Yeh KC, Kwan KC (1978) Comparison of numerical integrating algorithms by trapezoidal, Lagrange, and spline approximation. J Pharmacokinet Biopharm 6: 79–98
Riggs DS, Guarnieri JA, Addelman S (1978) Fitting straight lines when both variables are subject to error. Life Sci 22: 1305–1360
Hendeles L, Weinberger M, Bighley L (1977) Absolute bioavailability of oral theophylline. Am J Hosp Pharm 34: 525–527
Brodie BB, Axelrod J, and Reichenthal J (1952) Metabolism of theophylline (1,3-dimethylxanthine) in man. J Biol Chem 194: 215–222
Weinberger M, Ginchansky E (1977) Dose-dependent kinetics of theophylline dispoition in asthmatic children. J Pediatr 91: 820–824
Abernethy DR, Greenblatt DJ (1981) Impairment of antipyrine metabolism by low dose oral contraceptive steroids. Clin Pharmacol Ther 29: 106–110
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
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
Helton ED, Goldzieher JW (1977) The pharmacokinetics of ethynyl estrogens, a review. Contraception 15: 255–284
Levy G, Koysooko R (1976) Renal clearance of theophylline in man. J Clin Pharmacol 16: 329–332
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
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
O'Malley K, Stevenson IH, Crooks J (1972) Impairment of human drug metabolism by oral contraceptive steroids. Clin Pharmacol Ther 13: 552–557
Field B, Lu C, Hepner GW (1979) Inhibition of hepatic drug metabolism by norethindrone. Clin Pharmacol Ther 25: 196–198
Patwardhan RV, Desmond PV, Johnson RF, Schenker S (1980) Impaired elimination of caffeine by oral contraceptive steroids. J Lab Clin Med 95: 603–608
Lohmann SM, Miech RP (1976) Theophylline metabolism by rat liver microsomal system. J Pharmacol Exp Ther 196: 213–225
Hunt SN, Jusko WJ, Yurchak AM (1976) Effect of smoking on theophylline disposition. Clin Pharmacol Ther 19: 546–551
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
Landay RA, Gonzalez MA, Taylor JC (1978) Effect of phenobarbital on theophylline disposition. J Allergy Clin Immunol 62: 27–29
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
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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