**2.2 The PK-PG models**

Consist of mathematical expressions that describe the quantitative relationship between the drug dose necessary to achieve the same response intensity of a Biomarker or Surrogate Marker, for each one of the different genotypes phenotypically actives present in a population.

Pharmacogenetic models, PK-PG, are used to adapt the therapeutic use of different drugs to the idiosyncrasy of each patient and their genetic characteristics, increasing its efficiency and minimizing their side effects. Approximately 20-90% of the interindividual variability in drug response is consequence of individual genotype and variants that encode different polymorphs of the enzymes that metabolize and / or transport drugs.

Single Nucleotide Polymorphisms, SNPs, have been associated with substantial changes in the metabolism or in the effect of a drug, and therefore are being used to predict the clinical response to a drug of an individual. For the biotransformation of a drug, there are over 30 families of metabolizers enzymes belonging the family of cytochrome P-450, whose genetic polymorphisms normally lead to a functional changes in the encoded protein, resulting in individuals with different phenotypes:


Carrier proteins of drugs play an important role in regulating the absorption, distribution and excretion of many drugs. Within the ATP-binding cassette family, P-glycoprotein, encoded by the ABCB1 gene, is one of the best known , being its main function the control of the outflow from inside the cells of certain endogenous and / or exogenous substrates, including several drugs and substances such as bilirubin, so the presence of polymorphisms in this gene, entails changes in the PK and PD of certain drugs.
