Population Variations

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. 

2 h in adults and 16.3 h in geriatric patients. Lamivudine, an anti-HIV drug, has a half-life of only 2.0 h in pediatric patients (ages 4 months to 14 years). In adults with similar blood sampling, lamivudine has a tVi of 3.7 h.11 

Several interesting and representative trends are apparent in the data of Table 8.2. In terms of age, infants tend to have poorly developed metabolic function, but children have very high metabolic rates. Metabolism slows in adulthood and continues to decrease in geriatric patients. With regard to health problems, impaired liver function has the most dramatic effect on the half-life of theophylline relative to all the listed conditions. The impact of pregnancy is 

TABLE 8.2 Patient age and health effects on the half-life of theophylline 

Gender would seem to be an obvious and important difference among patients, but men and women have essentially the same metabolic activity when compared on a per mass basis. One very significant difference between men and women is that women can be pregnant. As was shown in Table 8.2, pregnancy can significantly impact a patient s metabolism. 

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Polar Coordinates. Yes, this is a type of factor space. We might use polar coordinates when we are mapping electron densities, seasonal population variations, or anytime it makes our work more convenient or allows us to better visualize or understand our data. 

Theoretical level populations. Sinee there are population variations on time seale shorter than some level lifetimes, a complete description of the excitation has been modeled solving optical Bloch equations Beacon model, Bellenger, 2002) at CEA. The model has been compared with a laboratory experiment set up at CEA/Saclay (Eig. 21). The reasonable discrepancy when both beams at 589 and 569 nm are phase modulated is very likely to spectral jitter, which is not modeled velocity classes of Na atoms excited at the intermediate level cannot be excited to the uppermost level because the spectral profile of the 569 nm beam does not match the peaks of that of the 589 nm beam. 

Giordani Soika, A., Perin, G. The pollution of the Venice lagoon study of chemical changes and population variations in the lagoon sediments in the last twenty years (in Italian) [29 Charts of the Venice lagoon], 1974. 

Wells, T. C. 1992. Population variation in North American Menziesia (Ericaceae). Ph.D. dissertation. University of British Columbia, Vancouver, B.C. 

The determination of an acceptable dose for humans involves the application of uncertainty factors to reflect the fact that, unlike the experimental animal, there is wide variability and susceptibility of response in the genetically diverse human population. Variations in gender, age, hormonal and disease status can affect the response to a chemical. In order to minimise any potential risks, uncertainty factors are applied to the NOAEL to arrive at a reduced exposure that is considered tolerable - namely the acceptable daily intake or ADI. These are usually tenfold for variations in susceptibility amongst the human population (the intra-species factor) and tenfold for the potential... 

Gasser, R.B., Monti, J.R., Bao-Zhen, Q., Polderman, A.M., Nansen, P. and Chilton, N.B. (1998) A mutation scanning approach for the identification of hookworm species and analysis of population variation. Molecular and Biochemical Parasitology 92, 303—312. 

Rollmann, S.M., Houck, L.D. and Feldhoff, R.C. (2000) Population variation in salamander courtship pheromones. J. Chem. Ecol. 26, 2713-2724. 

Population variation in salamander courtship pheromones. Journal of Chemical Ecology 26 2713-2724. 

Student s t a statistic used for testing differences in level between two sets of data when the variability of the dats is only estimate of the population variation... 

With the above caveat in mind, it is not difficult to understand that unimole-cular reactions can be activated by ambient blackbody radiation. This has been experimentally reported [44], Moreover, in this perspective, a chemical change would be closely related to a change (increase) in entropy via population variations in an ensemble. 

Marsh S, King CR, Porche-Sorbet RM, et al. Population variation in VKORKCI haplotype structure. J Thromb Haemost 2006 4 473-474. 

Interindividual differences in the levels of AHR mRNA in human peripheral blood lymphocytes have been reported to be small (64) however, little is known about population variation in AHR levels in other human tissues except for placenta where the receptor concentration is high in most subjects but not easily related to induction of CYP1A1 (33,65). The... 

Figure 6.6 Within- and between-population variation in desiccation resistance (A) and cuticular lipid quantity (B) as a function of body melanization in northern and southern Indian populations of Zaprionus indianus and Drosophila melanogaster. In both species, populations from drier (northern) habitats are more desiccation resistant. The desiccation-resistant population of D. melanogaster is melanic, whereas desiccation resistance in Z. indianus is correlated with higher amounts of surface lipids. From Parkash et al. (2008a) reproduced with permission.

Parkash, R., Kalra, B. and Sharma, V. (2008a). Changes in cuticular lipids, water loss and desiccation resistance in a tropical drosophilid - analysis of within population variation. Fly, 2,187-197. 

This approach usually involves a weighting of the amount and composition of hazardous material at each site, the contaminant characteristics of the site, the potential migration pathways, and the proximity of environmental or human populations. Variations of this approach have already been applied many times, either in a quasl-rigorous fashion or in a more general manner, as state and local authorities are faced with deciding where to concentrate limited resources. 

Adams, R.P. (1975) Gene flow versus selection pressure and ancestral differentiation in the composition of species analysis of population variation in Juniperus ashei Buch. using terpenoid data. /. Mol. Evol, 5,177-85. 

Miettinen, T. A. and Kesanlemi, Y.A., Cholesterol absorption regulation of cholesterol synthesis and elimination and within-population variation of serum cholesterol levels. Am. J. Clin. Nutr., 49, 629, 1989. 

Houle As an evolutionary biologist, I think there is an explicit connection between variation and the state of a population. Variation is how you got where you are now. You can t think about evolution without thinking about variation. This is a separate issue from Geoffrey s point, which is saying that making inferences about variation is part of what mental architecture must be about. 

While CASR variants contribute to monogenic disorders such as FHH and ADH, common CASR polymorphisms may also account for the observed population variation in calcium response that is a risk factor for a variety of disease susceptibilities. In fact,... 

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