Pharmacodynamic variability arises because of the relationship between drug concentration and effect. Within either instance, these specific genealogical variants enacting mediations pertaining to concentrations of drugs or their coinciding outcomes are increasingly being recognized as sources of variable drug action — ‘pharmacogenetics’ (Lin, 2007). Mutations, the changes in the sequences of genes in DNA, are one source of genetic variation (Lin, 2007). Another source is gene flow, or the movement of genes between different groups of organisms (Lin, 2007). Finally, genetic variation can result from sexual reproduction, which leads to the creation of new combinations of genes (Lin, 2007). When concerning responses towards administered drugs, differing populace, especially when involving ethnic vulnerability towards adverse drug reactions, are impacted when concerning polymorphisms residing within the genealogical scape. Genetic variation frequencies differ among different ethnicities, which may be associated with variation in susceptibility to adverse drug reactions among diverse populations. Variation in response to equivalent drug concentrations arises because of various factors, such as differences in receptor number and structure, receptor-coupling mechanisms, and physiological changes in target organs resulting from differences in genetics, age, and health (Lin, 2007).
Variations in drug response may be pharmacodynamic, implying inter-individual differences in the response of receptors in equal concentrations of the drug. In addition, it may also be pharmacokinetic, indicating that individuals receiving the same drug dose will have different drug concentrations in their body fluids (Hartmanshenn et al., 2016). Moreover, both inheritance and acquisition of either instance of variance are sure to follow. Variations in receptor sensitivity occur, but few inherited or acquired instances have well-documented clinical relevance. Should the therapeutic index reside at a decreased level or the causal relationship of the response as well as dosage does not retain a level of steepness, the concentration within the specific drug of the receptor region will not be critical, and causes of kinetic variation are unlikely to be clinically significant (Hartmanshenn et al., 2016). However, it is the many causes of kinetic variation, including effects due to drug formulation and changes in the absorption, distribution, metabolism, and excretion of drugs (Hartmanshenn et al., 2016). Analyzing and predicting variability due to these factors is desirable if consideration of dynamics suggests drug concentration will determine therapeutic efficacy.
Hartmanshenn, C., Scherholz, M., & Androulakis, I. P. (2016). Physiologically-based pharmacokinetic models: approaches for enabling personalized medicine. Journal of pharmacokinetics and pharmacodynamics, 43(5), 481-504.
Lin, J. H. (2007). Pharmacokinetic and pharmacodynamic variability: a daunting challenge in drug therapy. Current drug metabolism, 8(2), 109-136.
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