Sex Differences in Pharmacokinetics and Pharmacodynamics

Overview

Journal Clin Pharmacokinet

Specialty Pharmacology

Date 2009 Apr 24

PMID 19385708

Citations 381

Authors

Offie P Soldin

Donald R Mattison

Affiliations

Soon will be listed here.

Abstract

Significant differences that exist between the sexes affect the prevalence, incidence and severity of a broad range of diseases and conditions. Men and women also differ in their response to drug treatment. It is therefore essential to understand these reactions in order to appropriately conduct risk assessment and to design safe and effective treatments. Even from that modest perspective, how and when we use drugs can result in unwanted and unexpected outcomes. This review summarizes the sex-based differences that impact on pharmacokinetics, and includes a general comparison of clinical pharmacology as it applies to men, women and pregnant women. Sex-related or pregnancy-induced changes in drug absorption, distribution, metabolism and elimination, when significant, may guide changes in dosage regimen or therapeutic monitoring to increase its effectiveness or reduce potential toxicity. Given those parameters, and our knowledge of sex differences, we can derive essentially all factors necessary for therapeutic optimization. Since this is a rapidly evolving area, it is essential for the practitioner to review drug prescribing information and recent literature in order to fully understand the impact of these differences on clinical therapeutics.

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References

Anderson G . Sex differences in drug metabolism: cytochrome P-450 and uridine diphosphate glucuronosyltransferase. J Gend Specif Med. 2002; 5(1):25-33. View

Calabrese V . A micromethod for absorption of specific antibody using an enzyme-linked immunosorbent assay (ELISA). J Neurosci Methods. 1984; 11(2):137-41. DOI: 10.1016/0165-0270(84)90031-1. View

Umeh O, Currier J . Sex differences in pharmacokinetics and toxicity of antiretroviral therapy. Expert Opin Drug Metab Toxicol. 2006; 2(2):273-83. DOI: 10.1517/17425255.2.2.273. View

Tamai I, Saheki A, Saitoh R, Sai Y, Yamada I, Tsuji A . Nonlinear intestinal absorption of 5-hydroxytryptamine receptor antagonist caused by absorptive and secretory transporters. J Pharmacol Exp Ther. 1997; 283(1):108-15. View

Frezza M, Di Padova C, Pozzato G, Terpin M, BARAONA E, Lieber C . High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. N Engl J Med. 1990; 322(2):95-9. DOI: 10.1056/NEJM199001113220205. View

Aichhorn W, Whitworth A, Weiss E, Hinterhuber H, Marksteiner J . [Differences between men and women in side effects of second-generation antipsychotics]. Nervenarzt. 2006; 78(1):45-52. DOI: 10.1007/s00115-006-2112-0. View

BARAONA E, Abittan C, Dohmen K, Moretti M, Pozzato G, CHAYES Z . Gender differences in pharmacokinetics of alcohol. Alcohol Clin Exp Res. 2001; 25(4):502-7. View

Paolini M, Pozzetti L, Sapone A, Mesirca R, Perocco P, Mazzullo M . Molecular non-genetic biomarkers of effect related to acephate cocarcinogenesis: sex- and tissue-dependent induction or suppression of murine CYPs. Cancer Lett. 1997; 117(1):7-15. DOI: 10.1016/s0304-3835(97)00177-8. View

Duan L, Wang H, Ohashi A, Wang D . Role of intestinal sterol transporters Abcg5, Abcg8, and Npc1l1 in cholesterol absorption in mice: gender and age effects. Am J Physiol Gastrointest Liver Physiol. 2005; 290(2):G269-76. DOI: 10.1152/ajpgi.00172.2005. View

10.

Harris R, Tsunoda S, Mroczkowski P, Wong H, Benet L . The effects of menopause and hormone replacement therapies on prednisolone and erythromycin pharmacokinetics. Clin Pharmacol Ther. 1996; 59(4):429-35. DOI: 10.1016/S0009-9236(96)90112-5. View

11.

Caballeria J, BARAONA E, Rodamilans M, Lieber C . Effects of cimetidine on gastric alcohol dehydrogenase activity and blood ethanol levels. Gastroenterology. 1989; 96(2 Pt 1):388-92. DOI: 10.1016/0016-5085(89)91562-x. View

12.

Stephen A, Wiggins H, Englyst H, Cole T, Wayman B, Cummings J . The effect of age, sex and level of intake of dietary fibre from wheat on large-bowel function in thirty healthy subjects. Br J Nutr. 1986; 56(2):349-61. DOI: 10.1079/bjn19860116. View

13.

Cooper S, Drolet D, Dugal R . Comparative bioavailability of two oral formulations of flurazepam in human subjects. Biopharm Drug Dispos. 1984; 5(2):127-39. DOI: 10.1002/bdd.2510050206. View

14.

Shah A, Scott N, Morse T, Apseloff G . Pharmacokinetics and safety of oral eletriptan during different phases of the menstrual cycle in healthy volunteers. J Clin Pharmacol. 2002; 41(12):1339-44. DOI: 10.1177/00912700122012922. View

15.

Cunningham J . Body composition and resting metabolic rate: the myth of feminine metabolism. Am J Clin Nutr. 1982; 36(4):721-6. DOI: 10.1093/ajcn/36.4.721. View

16.

Butera L, Feinfeld D, Bhargava M . Sex differences in the subunits of glutathione-S-transferase isoenzyme from rat and human kidney. Enzyme. 1990; 43(4):175-82. DOI: 10.1159/000468728. View

17.

Greenblatt D, Shader R, Franke K, MacLaughlin D, Ransil B, Koch-Weser J . Kinetics of intravenous chlordiazepoxide: sex differences in drug distribution. Clin Pharmacol Ther. 1977; 22(6):893-903. DOI: 10.1002/cpt1977226893. View

18.

Seitz H, Egerer G, Simanowski U, Waldherr R, Eckey R, Agarwal D . Human gastric alcohol dehydrogenase activity: effect of age, sex, and alcoholism. Gut. 1993; 34(10):1433-7. PMC: 1374557. DOI: 10.1136/gut.34.10.1433. View

19.

Mattison D, Blann E, Malek A . Physiological alterations during pregnancy: impact on toxicokinetics. Fundam Appl Toxicol. 1991; 16(2):215-8. DOI: 10.1016/0272-0590(91)90103-b. View

20.

Barnas C, Slimko J, Schwartz J . Faster clearance of sustained release verapamil in men versus women: continuing observations on sex-specific differences after oral administration of verapamil. Clin Pharmacol Ther. 2000; 68(3):286-92. DOI: 10.1067/mcp.2000.109356. View