Metabolism gender factors

While cotinine functions fairly well as a marker of nicotine intake, it is not perfect due to individual variation in metalxtlism as discussed previously. As described earlier in this chapter, cotinine metabolism is affected by factors such as race, gender, age, genetic variation in the liver enzyme CYP2A6, and/or by the presence of pregnancy, liver or kidney disease. Another limitation to the use of cotinine is that, given an average half-life of 16 h, cotinine levels reflect relatively short-term exposure to tobacco (that is, over the past 3 days). 

Humans differ in sensitivity due to biological factors such as metabolic polymorphism, age, gender, health status, and nutritional status. These differences can be the result of genetic and/or environ-mental/behavioral influences. This intraspecies (interindividual) variation is greater in humans than in the more inbred experimental animal population. 

Special populations Use a starting dose of 6 mg/25 mg for patients with a predisposition to hypotensive reactions, patients with hepatic impairment, or patients who exhibit a combination of factors that may slow the metabolism of olanzapine/fluoxetine (eg, female gender, elderly, nonsmoking status). When indicated, perform dose escalation with caution in these patients. Olanzapine/fluoxetine has not been systemically studied in patients older than 65 years of age or in patients younger than 18 years of age. 

Yoshii, F., Barker, W.W., Chang, J.Y., Loewenstein, D.. Apicella, A., Smith, D.. et al. Sensitivity of cerebral glucose metabolism to age, gender, brain volume, brain atrophy, and cerebrovascular risk factors. J. Cerebr. Blood Flow Metab. 8(5), 654-661, 1988. 

Many differences in overall toxicity between males and females of various species are known (Table 9.1). Although it is not always known whether metabolism is the only or even the most important factor, such differences may be due to gender-related differences in metabolism. Hexobarbital is metabolized faster by male rats thus female rats have longer sleeping times. Parathion is activated to the cholinesterase inhibitor paraoxon more rapidly in female than in male rats, and thus is more toxic to females. Presumably many of the gender-related differences, as with the developmental differences, are related to quantitative or qualitative differences in the isozymes of the xenobiotic-metabolizing enzymes that exist in multiple forms, but this aspect has not been investigated extensively. 

Not all patients are the same. Patients differ in their age, gender, genetics, and health. All these factors can play a role in drug metabolism. Metabolism rate is evaluated through the basic pharamacokinetic parameters of Vd, CL, kel, and tl/2 (Chapter 7). Of course, to show variability in metabolism, a drug must first be metabolized. Some drugs are eliminated unchanged. 

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. 

Interspecies and interindividual variability in drug metabolism is influenced by both genetic and environmental factors. The basal rate of drug metabolism in a particular individual is determined primarily by genetic constitution, but also varies with age, gender, and environmental factors such as diet, disease states, and concurrent use of other drugs. 

This descriptive statistic will be presented by CYP 2C19 metabolizer-status and where applicable by gender, including mean (arithmetic and/or geometric), standard deviation (usual and/or dispersion factor), standard error of the mean, coefficient of variation (in %), median, minimum, maximum, number of observations. 

Moreover, major influences on the metabolism of xenobiotics in the liver due to nutritional factors as well as through interactions with chemicals and alcohol have been reported. Distinct age and gender-related differences have also been noted, (s. tab. 3.18) The glucuro-... 

The clinical course can be unfavourably affected by various risk factors (e.g. race, gender, advanced age, immune status, genetics) as well as by alcohol abuse (275, 337, 363), toxins, coinfections and chemicals. Conversely, the course and prognosis of HBV, HDV and HIV infections as well as of metabolic diseases (e.g. porphyria cutanea tarda, ai-antitrypsin deficiency) can deteriorate as a result of hepatitis C. 

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