Gender, metabolic effects

Gender-related effects have been evaluated for trazodone, and clearance is lower for elderly men compared with elderly women [D. J. Greenblatt et al. 1987]. Differences exist in the metabolic rate of the SRI sertraline [Warrington 1991]. The effect of OCs on the pharmacokinetics of SRls or... 

Vassileva G, Hu W, Hoos L, et al. Gender-dependent effect of Gpbarl genetic deletion on the metabolic profiles of diet-induced obese mice. 7 Endocrinol. 2010 205 225-232. 

Perkins KA, Donny E, et al (1999) Sex differences in nicotine effects and self-administration review of human and animal evidence. Nicotine Tob Res 1(4) 301-315 Perkins KA, Epstein EH, et al (1991) Effects of dose, gender, and level of physical activity on acute metabolic response to nicotine. Pharmacol Biochem Behav 40(2) 203-208 Perkins KA, Epstein EH, et al (1992) Effects of nicotine on hunger and eating in male and female smokers. Psychopharmacology 106(l) 53-59... 

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. 

Once a chemical enters the body of animal or human, it undergoes metabolic reaction. A host of factors modulate the reaction rate and the induction of toxicological effects. These factors have been termed intrinsic factors and include animal species, gender, age, nutritional status, pregnancy, other health status, and circadian rhythms. In addition, there are certain extrinsic factors (e.g., physicochemical properties of chemicals, solvent or vehicle, route of exposure, temperature, and humidity) during exposure to chemicals that also influence the effect of a test chemical. We shall discuss these factors in greater detail. 

Animal Gender Role of gender and metabolism of xenobiotics has been studied in a variety of experimental animals, particularly rats. The toxicological effects of many chemicals have shown differences between male and female animals. A classic example is the acute toxicity data of different pesticides between male and female rats. This difference was found both when animals were exposed by ingestion or dermal absorption. The ratio between male and female in oral LD50 values for of chemicals (e.g., pesticides) ranges from 0.21 to 4.62, which... 

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... 

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