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Relationship Between Pharmacokinetics and Pharmacogenomics and Its Impact on Drug Choice and Dose Regimens

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ADME Processes in Pharmaceutical Sciences

Abstract

Plasmatic levels of a drug may suffer variations due to a) medication-associated factors, such as problems in the disintegration or dissolution process, or differences in the release from the pharmaceutical form; b) pathophysiological changes, such as variation in the gastric or plasmatic pH which could modify the ionized fraction of the drug, or a decrease in the intestinal motility could affecting drug absorption; and c) interactions with food or with other medications, for example, fluoroquinolones as ciprofloxacin administered together with milk decreases the absorption of the antibiotic by chelation with calcium, or inhibition of P-glycoprotein by verapamil increases digoxin bioavailability and toxicity. Besides, genetic and epigenetic factors could generate inter-individual variations in the pharmacokinetics/pharmacodynamics processes affecting every one of ADME stages. A dysfunctional efflux pump in the enteric membrane could increase the toxicity of some drugs, alterations in protein binding sites could affect the distribution, a SNP, duplication or deletion in a gene that encodes a metabolizing enzyme could increase or decrease the plasmatic concentration of some drugs affecting their therapeutic effect, and an overexpression of a transporter in the apical membrane in the renal tubules can lead to enhance elimination, decreasing the drug half-life. In this chapter, we will review basic concepts of genetics, how changes in genes can affect pharmacokinetic processes and the influence of pharmacogenetics in clinical practice.  

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Authors and Affiliations

  1. Laboratory of Chemical Carcinogenesis and Pharmacogenetic (CQF), Department of Basic and Clinical Oncology (DOBC), Faculty of Medicine, University of Chile & Latin American Society of Pharmacogenomics and Personalized Medicine (SOLFAGEM), Santiago, Chile

    Matías F. Martínez & Luis A. Quiñones

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  1. Matías F. Martínez
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  2. Luis A. Quiñones
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Correspondence to Luis A. Quiñones .

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  1. Laboratory of Bioactive Research and Development (LIDeB), Department of Biological Sciences, Faculty of Exact Sciences, University of La Plata (UNLP), La Plata, Buenos Aires, Argentina

    Alan Talevi

  2. Quality Control of Pharmaceutical Products, Pharmaceutical Toxicology, Department of Biological Sciences, Faculty of Exact Sciences, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina

    Pablo A. M. Quiroga

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Martínez, M.F., Quiñones, L.A. (2018). Relationship Between Pharmacokinetics and Pharmacogenomics and Its Impact on Drug Choice and Dose Regimens. In: Talevi, A., Quiroga, P. (eds) ADME Processes in Pharmaceutical Sciences. Springer, Cham. https://doi.org/10.1007/978-3-319-99593-9_8

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