Pharmacokinetics genetic variations

Ethnic differences have been shown to influence response to psychotropic medications. Much of the focus on the explanation for such differences has been on drug-metabolizing (CYP) enzymes of the liver and their sway over pharmacokinetic factors. It is now well recognized that differences in the distribution of polymorphic variants of CYP enzymes exist between different ethnic groups. However, within ethnic groups there are considerable inter-individual variations in drug kinetics, which may not be accounted for solely by genetic variation. Responses to pharmacotherapy are multifaceted and involve the interaction of environmental and... 

Pharmacokinetic modeling, 208 Pharmacokinetics (PK), 99, 211 Pharmacologic agents, variation in response to, 43 Pharmacologic research, 31 Pharmacology, genetic variation and, 36-38... 

While other factors (e.g., existing disease, concomitant medication, nutrition, and use of tobacco and alcohol) can influence why different people respond differently to a given drug, the predominant factor is genetic variation, specifically variation in the structure of the target receptor and in pharmacokinetics (Primrose and Twyman, 2006). 

We have discussed both target receptors and pharmacokinetics in this book. Protein manufacture is under direct genetic control, and two factors are of particular relevance here. First, the precise structure and function of protein macromolecules (receptors) targeted by a specific drug molecule will vary in different individuals. Since the structure and function of the protein are directly related to how the drug molecule will interact with that protein, individuals responses to the drug will vary. Second, there are genetic variations in metabolic enzymes (proteins) and hence metabolism. Both of these processes fall neatly into the domain of pharmacoproteomics (see Section 14.8). 

Gong IY, Rim RB (2013) Impact of genetic variation in OATP transporters to drug disposition and response. Drug Metab Pharmacokinet 28 4-18... 

Mizuno T, Fukudo M, Terada T, Kamba T, Nakamura E, Ogawa O, Inui K, Katsura T (2012) Impact of genetic variation in breast cancer resistance protein (BCRP/ABCG2) on sunitinib pharmacokinetics. Drug Metab Pharmacokinet 27 631-639... 

Adkison KK, Vaidya SS, Lee DY, Koo SH, Li L, Mehta AA, Gross AS, Polli JW, Humphreys JE, Lou Y, Lee EJ (2010) Oral sulfasalazine as a clinical BCRP probe substrate pharmacokinetic effects of genetic variation (C421A) and pantoprazole coadministration. J Pharm Sci 99 1046-1062... 

Pharmacogenetics involves the impact of genetic variation on drug response. The link between genetically determined variation in drug metabolism enzymes (e.g., cytochrome p450, N-acetyltransferase) and intersubject differences in pharmacokinetics is well established. Likewise, there is an increasing awareness that differences in transporter expression can impact the efficacy and safety of pharmacotherapy. 

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