Pharmacogenetics: pharmacokinetics and clinical implications
Blardi, P.
Recenti Progressi in Medicina 88(1): 46-55
1997
ISSN/ISBN: 0034-1193 PMID: 9102716 Document Number: 469557
In the last years, pharmacogenetic studies tried to identify the hereditary bases characterizing different individual response to drugs. Human organism tries to remove drugs by activating enzyme systems. Metabolization reaction rate shows wide interindividual variations, being characterized by different factors, such as physiologic (age, sex), pathologic (liver and kidney diseases), and genetic characteristics. Inborn errors may lead to some alterations in functional enzyme activities. These alterations led to divide the whole population into two groups: slow metabolizers PM (having a slow metabolism), and fast metabolizers EM (having a normal metabolism). Such a different behaviour may lead to changes in pharmacokinetic parameters which may also influence pharmacodynamic characteristics of the drug, thus leading to: 1) an excessive therapeutic effect, 2) a decreased therapeutic effect, 3) an increased toxicity of the drug not undergoing its transformation, 4) toxicity of a metabolic byproduct formed by a pathway different from the main one.