Metabolism gender differences

A brief review of pharmacokinetic principles will place the available data on gender differences in context. Bioavailability, which refers to the amount of drug eventually reaching the systemic circulation, is influenced by absorption, metabolism in the gastrointestinal tract, and the hepatic first-pass effect. The impact of the first-pass effect is greater for drugs that have high hepatic... 

After the drug is absorbed, it may be taken up by hepatocytes and metabolized, a process that is referred to as the hepatic first-pass effect. If the compound is highly extractable, then the amount of drug removed is high and the degree of available drug is lowered. It is not known whether there are gender differences in hepatic blood flow that can influence the extraction rate of some medications. 

Schmidt. M.E., Matochik, J.A., Goldstein, D.S., et al. Gender differences in brain metabolic and plasma catecholamine responses to alpha2-adrenoceptor blockade. 

Hayes FJ, Fiad TM, McKenna TJ. Gender difference in the response of growth hormone (GH)-deficient adults to GH therapy. Metabolism 1999 48(3) 308-13. 

Drug Discovery Today 7 25-27 Li AP (2004) In vitro approaches to evaluate ADMET drug properties. Curr Top Med Chem 4 701-706 Li W, Escarpe PA, Eisenberg EJ et al. (1998) Identification of GS 4104 as an orally bioavailable prodrug of the influenza virus neuraminidase inhibitor GS 4071. Antimicrobial Agents and Chemotherapy 42 647-653 Los LE, Welsh DA, Herold EG et al. (1996) Gender differences in toxicokinetics, liver metabolism, and plasma esterase activity observations from a chronic (27-week) toxicity study of enalapril/diltiazem combinations in rats. Drug Metab Dispos 24 28-33... 

Los LE, Welsh DA, Herold EG et al. (1996) Gender differences in toxicokinetics, liver metabolism, and plasma esterase activity observations from a chronic (27-week) toxicity study of enalapril/ditiazem combinations in rats. Drug... 

Rane A (1999) Phenotyping of drug metabolism in infants and children Potentials and problems. Pediatrics 104 640-643 Relling MV, Lin JS, Ayers GD, Evans EE (1992) Racial and gender differences in N-acetyltransferase, xanthine oxidase and CYP1A2 activities. Clin Pharmacol Ther 52 643-658... 

The gender difference in pellagra (Section 8.5) suggests that endogenous estrogens may have an effect on tryptophan metabolism similar to tbat of exogenous estrogens used as contraceptives. It implies that not only is the... 

An example of the gender dilemma is illustrated in systemic lupus erythematosus (SLE) an autoimmune disease that occurs more frequently in women than men. The gender difference is attributed to differences in the metabolism of sex hormones or regulation by gonadotropin releasing hormone (GnRH). When it occurs in men, SLE tends to be more severe (Yacoub Wasef, 2004). Recent studies also indicate that SLE may be more common in nonwhite women of child bearing... 

Species/gender differences in tumor incidence, toxicokinetics (AUC), protein binding, and metabolism... 

---