Skip to main content
SpringerLink
Log in

Influence of Sex on Drug Kinetics in Man

  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

Very few investigations in man have been specifically devoted to the influence of sex on drug kinetics. Although the potential role of various factors such as the phase of the menstrual cycle, hormonal steroid contraceptive use, menopause or andropause is virtually never taken into account, sex-linked differences in drug kinetics do exist for a limited number of substances such as certain antibiotics, a few tricyclic antidepressants, lithium and aspirin. These sex-linked differences are relatively minor from a quantitative standpoint and appear to be due chiefly to differences in body composition and activity of circulating enzymes and hormones. On the basis of present knowledge, in general these differences in drug kinetics do not warrant modifying dosage as a function of sex.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Birch, N.J.; Greenfield, A.A. and Hullin, R.P.: A metabolic profile of patients receiving prophylactic lithium therapy. British Journal of Pharmacology 52: 443P–444P (1974).

    Google Scholar 

  • Bird, C.E. and Clark, A.F.: Kinetics of 3H-5-dihydrotestosterone metabolism in normal men and women and men with prostatic carcinoma; effects of estrogen administration in men. Journal of Clinical Edocrinology and Metabolism 34: 467–472 (1972).

    Article  CAS  Google Scholar 

  • Bjorntorp, P.; Bengtsson, C.; Blohme, G.; Jonsson, A.; Sjostrom, L.; Tibblin, E.; Tibblin, G. and Wilhelmsen, L.: Adipose tissue fat cell size and number in relation to metabolism in randomly selected middle-aged men and women. Metabolism 20; 927–935 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Blecher, T.E.; Edgar, W.M.; Melville, H.A.H. and Peel, K.R.: Transplacental passage of ampicillin. British Medical Journal 1: 137–139 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Briggs, M.H.; Vitamin A and the teratogenic risks of oral contraceptives. British Medical Journal 3: 170–171 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Buckingham, M.; Welply, G.; Miller, J.F. and Elstein, M.: Gastrointestinal absorption and transplacental transfer of amoxycillin during labour and the influence of metoclopramide. Current Medical Research and Opinion 3: 392–396 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Burrows, G.; Scoggins, B.A.; Turecek, L.R. and Davies, B.: Plasma nortriptyline and clinical response. Clinical Pharmacology and Therapeutics 16: 639–644 (1974).

    PubMed  CAS  Google Scholar 

  • Clark, A.F.; Calandra, R.S. and Bird, C.E.: Binding of testosterone and 5-α-dihydrotestosterone to plasma proteins in humans. Clinical Biochemistry 4: 89–96 (1971).

    Article  CAS  Google Scholar 

  • Crawford, J.S. and Rudofsky, S.: Some alterations in the pattern of drug metabolism associated with pregnancy, oral contraceptives and the newly born. British Journal of Anaesthesia 38: 446–454 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Davison, J.S.; Davison, M.C. and Hay, D.M.: Gastric emptying time in late pregnancy and labour. Journal of Obstetrics and Gynaecology of the British Commonwealth 77: 37–41 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Donatelli, L.: Eta, sesso e barbiturismo acuto. Contributo chemico e sperimentale. Archives Internationales de Pharmacodynamic et de Therapie 74: 90–111 (1947).

    CAS  Google Scholar 

  • Eadie, M.J.; Tyrer, J.H. and Hooper, W.D.: Diphenylhydantoin dosage. Proceedings of the Australian Association of Neurology 10: 53–59 (1973).

    CAS  Google Scholar 

  • Fisher, A.M. and Smith, M.R.: The prophylactic use of ampicillin and its transplacental passage after amniotomy. Journal of Obstetrics and Gynaecology of the British Commonwealth 74: 855–861 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Fishman, J.L.; Boyar, R.M. and Hellman, L.: The system estradiol-estrone: a sex difference in oxidation of estradiol in man. Journal of Clinical Endocrinology and Metabolism 34: 989–996 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Fraser, H.S.; Bulpitt, C.J.; Kahn, C.; Mould, G.; Mucklow, J.C. and Dollery, C.T.: Factors affecting antipyrine metabolism in West African villagers. Clinical Pharmacology and Therapeutics 20: 369–376 (1976).

    PubMed  CAS  Google Scholar 

  • Giudicelli, J.F.; Richer, C.; Berdeaux, A. and Guessous, N.: Influence of sex on the clinical pharmacology of flutiorex, a new anorectic drug. Eur. J. Clin. Pharmacol. 10: 325–330 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Gordon, G.G.; Altman, K.; Southern, A.L. and Olivo, J.: Human hepatic testosterone A-ring reductase activity: effect of medroxyprogesterone acetate Journal of Clinical Endocrinology and Metabolism 32: 457–461 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Grant, E.C.G. and Mears, E.: Mental effects of oral contraceptives. Lancet 3: 945–946 (1967).

    Article  Google Scholar 

  • Graupner, K.: Uber einen Untershied der Lokalanaesthetischen Wirkung von Lidocain am der Cornea mannlicher und weiblicher Versuchspersonen. Medicina experimentalis 10: 111–114 (1964).

    PubMed  CAS  Google Scholar 

  • Grossman, M.I.; Kirsner, J.B. and Gillespie, I.A.: Basal and Histalog-stimulated gastric secretion in control subjects and in patients with peptic ulcer or gastric cancer. Gastroenterology 45: 14–26 (1963).

    PubMed  CAS  Google Scholar 

  • Hammer, W. and Sjoqvist, F.: Plasma levels of monomethylated tricyclic antidepressants during treatment with imipramine-like compounds. Life Sciences 6: 1895–1903 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Hellman, L.; Zumoff, B.; Kessler, G.; Kara, E.; Rubin, I.L. and Rosenfield, R.S.: Reduction of cholesterol and lipids in man by ethyl-p-chlorophenoxy-isobutyrate. Annals of Internal Medicine 59: 477–494 (1963).

    PubMed  CAS  Google Scholar 

  • Hooper, W.D.; Bochner, F.; Eadie, M.J. and Tyrer, J.H.: Plasma protein binding of diphenylhydantoin. Effects of sex hormones, renal and hepatic diseases. Clinical Pharmacology and Therapeutics 15: 276–282 (1974).

    PubMed  CAS  Google Scholar 

  • Houghton, G.W.; Richens, A. and Leighton, M.: Effects of age, height, weight and sex on serum phenytoin concentration in epileptic patients. British Journal of Clinical Pharmacology 2: 251–256 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Huffman, D.H.; Shoeman, D.W.; Pentikainen, P. and Azamoff, D.L.: The effect of spironolactone on antipyrine metabolism in man. Pharmacology 10: 338–344 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Hurwitz, N.: Predisposing factors in adverse reactions to drugs. British Medical Journal 1: 536–539 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Iwainsky, H.; Winsel, K.; Werner, E. and Eule, H.: On the pharmacokinetics of rifampicin during treatment with intermittent administration. II. Influence of age and sex of the patients. Scandinavian Journal of Respiratory Diseases 57: 5–11 (1976).

    PubMed  CAS  Google Scholar 

  • Jacobs, A.: Sex differences in iron absorption. Proceedings of the Nutrition Society 35: 159–162 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Johnsen, S.G.; Kampmann, J.P.; Bennett, E.P. and Jorgensen, F.S.: Enzyme induction by oral testosterone. Clinical Pharmacology and Therapeutics 20: 233–237 (1976).

    CAS  Google Scholar 

  • Juhlin, I.: Problems in diagnosis, treatment and control of gonorrhoeal infections. Acta Dermato-Venereologica 45: 231–241 (1965).

    PubMed  CAS  Google Scholar 

  • Kampmann, J.; Molmholm-hansen, J.; Siersbaek-Nielsen, K. and Kristensen, M.: Serum creatinine and drug half-lives. Journal of the American Medical Association 223: 193 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Kellermann, G.; Luyten-Kellermann, M.; Horning, M.G. and Stafford, M.: Elimination of antipyrine and benzo: a: pyrene metabolism in cultured human lymphocytes. Clinical Pharmacology and Therapeutics 20: 72–80 (1976).

    PubMed  CAS  Google Scholar 

  • Koch-Weser, J. and Sellers, E.M.: Drug interactions with coumarin anticoagulants. New England Journal of Medicine 285: 547–558 (1971).

    Article  CAS  Google Scholar 

  • Loh, H.S.; Odumosu, A. and Wilson, C.W.M.: Factors influencing the metabolic availability of ascorbic acid. I. The effect of sex. Clinical Pharmacology and Therapeutics 16: 390–408 (1974).

    PubMed  CAS  Google Scholar 

  • McQueen, E.G.: Pharmacological basis of adverse drug reactions; in Avery (Ed) Drug Treatment, p. 169 (ADIS Press, Sydney; Publishing Sciences Group, Acton, Mass; Churchill Livingstone, Edinburgh 1976).

    Google Scholar 

  • Martin, J.F.; Mikulecky, M.; Blaschike, J.F.; Waggoner, J.G.; Vergalla, J. and Berk, P.D.: Difference between the plasma indocyanine disappearance rates of normal men and women. Proceedings of the Society for Experimental Biology and Medicine 150: 612–617 (1975).

    PubMed  CAS  Google Scholar 

  • Mather, L.E.; Tucker, G.T.; Pflug, A.E.; Lindop, M.J. and Wilkerson, C.: Meperidine kinetics in man. Intravenous injection in surgical patients and volunteers. Clinical Pharmacology and Therapeutics 17: 21–30 (1975).

    PubMed  CAS  Google Scholar 

  • Menguy, R.; Desbaillets, L.; Masters, Y.F. and Okabe, S.: Evidence for a sex-linked difference in aspirin metabolism. Nature 239: 102–103 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Moody, J.P.; Tait, A.C. and Todrick, A.: Plasma levels of imipramine and desmethylimipramine during therapy. British Journal of Psychiatry 113: 183–193 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Nielsen, B.; Sorensen, A.W.; Szabo, L.; Pedersen, E.. and Scharff, A.: Kanamycin serum half-life and renal function: age and sex. Danish Medical Bulletin 20: 144–149 (1973).

    PubMed  CAS  Google Scholar 

  • Nimmo, W.S.: Drugs diseases and altered gastric emptying. Clinical Pharmacokinetics 1: 189–203 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Novak, L.P.: Ageing, total body potassium, fat free mass and cell mass in males and females between the ages 18 and 85 years. Journal of Gerontology 27: 438–443 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Odumosu, A. and Wilson, C.W.: The buccal absorption of vitamin C. Proceedings of the Nutrition Society 30: 81A–82A (1971).

    PubMed  CAS  Google Scholar 

  • O’Malley, K.; Crooks, J.; Duke, E. and Stevenson, I.H.: Effects of age and sex on human drug metabolism. British Medical Journal 3: 607–609 (1971).

    Article  PubMed  Google Scholar 

  • O’Malley, K.; Stevenson, I.H. and Crooks, J.: Impairment of human drug metabolism by oral contraceptive steroids. Clinical Pharmacology and Therapeutics 13: 552–557 (1972).

    PubMed  Google Scholar 

  • Perrier, D. and Gibaldi, M.: Estimation of drug elimination in renal failure. Journal of Clinical Pharmacology 13: 458–462 (1973).

    PubMed  CAS  Google Scholar 

  • Prescott, I.F.: Gastrointestinal absorption of drugs. Medical Clinics of North America 48: 907–916 (1974).

    Google Scholar 

  • Proven, G. and Canetti, G.: Les taux de rifampicine dans le serum de l’Homme. Revue de la Tuberculose (Paris) 32: 707–716 (1968).

    Google Scholar 

  • Quinn, G.P.; Axelrod, J. and Brodie, B.B.: Species, strain and sex differences in metabolism of hexobarbitone, amidopyrine, antipyrine and aniline. Biochemical Pharmacology 1: 152–159 (1958).

    Article  Google Scholar 

  • Raskin, A.: Age-sex differences in response to antidepressant drugs. Journal of Nervous and Mental Diseases 159: 120–130 (1974).

    Article  CAS  Google Scholar 

  • Robinson, B.H.B.; Hawkins, J.B.; Ellis, J.E. and Moore-Robinson, M.: Decreased antucoagulant tolerance with oxymetholone. Lancet 1: 1356 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Saez, J.M.; Forest, M.G.; Morera, A.M. and Bertrand, J.: Metabolic clearance rate and blood production rate of testosterone and dihydrotestosterone in normal subjects during pregnancy and in hyperthyroidism. Journal of Clinical Investigation 51: 1226–1234 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Sato, A.; Nakajima, T.; Fukiwara, Y. and Murayama, N.: Kinetic studies on sex difference in susceptibility to chronic benzene intoxication, with special reference to body fat content. British Journal of Industrial Medicine 32: 321–328 (1975).

    PubMed  CAS  Google Scholar 

  • Schroder, G.; Abrahamsson, L.; Wasser, A.; Malmcrona, R. and Bergquist, N.: Digoxin: plasma concentration of digoxin in out-patients. Acta Medica Scandinavica 193: 215–218 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Schrogie, J.J.; Solomon, H.M. and Zieve, P.D.: Effects of oral contraceptives on vitamin K-dependent clotting activity. Clinical Pharmacology and Therapeutics 8: 670–675 (1967).

    PubMed  CAS  Google Scholar 

  • Scotti, R.: Sex differences in blood levels of some antibiotics. Chemotherapy 18: 205–211 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Sherwin, A.L.; Loynd, J.S.; Bock, G.W. and Sokolowski, C.B.: Effects of age, sex, obesity and pregnancy on plasma diphenylhydantoin levels. Epilepsia 15: 507–521 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Somani, S.M. and Khurana, R.C.: Mechanism of estrogen-ipramine interaction. Journal of the American Medical Association 223: 560 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Sotaniemi, E.A. and Huhti, E.: Half-life of intravenous tolbutamide in the serum of patients in medical wards. Annals of Clinical Research 6: 146–154 (1974).

    PubMed  CAS  Google Scholar 

  • Stern-Nielsen, L.K. and Friis, T.: Tyroksinomsaetningens aldersafhaengighed hos eutyreoide patienter. Ugeskrift for Laeger 135: 640–644 (1973).

    Google Scholar 

  • Travers, R.; Reynolds, E.H. and Callagher, B.: Variation in response to anticonvulsants in a group of epileptic patients. Archives of Neurology 27: 29–33 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Tryding, N.E.; Nilsson, S.E.; Tufvesson, G.; Berg, R.; Carlstrom, S.; Elmfors, B. and Nilsson, J.E.: Physiological and pathological influence on serum monoamine oxidase levels. Effect of age, sex, contraceptive steroids and diabetes mellitus. Scandinavian Journal of Laboratory Investigation 23: 79–84 (1969).

    Article  CAS  Google Scholar 

  • Vermeulen, A. and Verdonk, L.: Studies on the binding of testosterone in human plasma. Steroids 11: 609–619 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Vesell, E.S. and Page, JG.: Genetic control of drug levels in man: phenylbutazone. Science 159: 1479–1480 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Villeneuve, A.; Gautier, J.; Jus, A. and Perron, D.: Effect of lithium on thyroid in man. Lancet 2: 502 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Vukovich, R.A.; Brannick, L.H.; Sugerman, A.A. and Neiss, E.S.: Sex differences in the intramuscular absorption and bioavailability of cephradine. Clinical Pharmacology and Therapeutics 18: 215–220 (1975).

    PubMed  CAS  Google Scholar 

  • Weiner, M.; Siddiqui, A.A.; Bostanci, N. and Dayton, P.G.: Drug interactions: the effect of combined administration on the half-life of coumarin and pyrazolone drugs in man. Federation Proceedings 24: 153 (1965).

    Google Scholar 

  • Weiner, M.; Siddiqui, A.A.; Shahani, R.T. and Dayton, P.G.: Effects of steroids on disposition of oxyphenbutazone in man. Proceedings of the Society for Experimental Biology and Medicine 124: 1170–1173 (1967).

    PubMed  CAS  Google Scholar 

  • Whittaker, J.A. and Price-Evans, J.A.: Genetic control of phenylbutazone in man. British Medical Journal 4: 323–328 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Wild, J.; Schorah, C.J. and Smithells, R.W.: Vitamin A, pregnancy and oral contraceptives. British Medical Journal 1: 57–59 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Ziegler, D.M. and Gold, M.S.: Oxidative metabolism of tertiary amine drugs by human liver tissue. Xenobiotica 1: 325–326 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Zumoff, B.; Bradlow, H.L. and Hellman, L.: 17-oxidation of testosterone in man: absence of a sex difference. Journal of Clinical Endocrinology and Metabolism 37: 293–296 (1973).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departements de Pharmacologie, Facultes de Medecine de Paris-Sud et de Paris-Val de Marne, Paris, France

    J. F. Giudicelli & J. P. Tillement

Authors
  1. J. F. Giudicelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. P. Tillement
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Giudicelli, J.F., Tillement, J.P. Influence of Sex on Drug Kinetics in Man. Clin Pharmacokinet 2, 157–166 (1977). https://doi.org/10.2165/00003088-197702030-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-197702030-00001

Keywords

Search

Navigation