[II. Pharmacogenetics--the future of modern pharmacology and genetics]

Med Wieku Rozwoj. 2004 Oct-Dec;8(4 Pt 1):967-91.
[Article in Polish]

Abstract

Pharmacogenetics is a scientific discipline connecting pharmacology and genetics. Its point of interest is an analysis of the variable, genetically determined patient's response to drugs. The basic discovery in this field was the elucidation of the heterogenic response of patients to the tuberculostatic drug -- isoniazid. The new era of searching for the molecular background of the variable drugs metabolism has begun after identification, in the 50's, of the polymorphic variants of NAT2 gene. It encodes for N-acetyltransferase 2, an isoniazid metabolizing enzyme. The key catalysts of the biotransformation reactions are cytochrome P450 isoenzymes. Identification of the polymorphic variants of genes encoding these enzymes enabled an explanation of the heterogenic drugs tolerance. The current knowledge shows that the genetic defects that are responsible for variable pharmacological response concern not only genes encoding the metabolising enzymes but also transporter proteins and drug receptors. Due to achievements of the molecular genetics and putting into practice the modern bioinformatic technics new pharmacological opportunities have been created. It becomes possible to predict the patient's individual reactions and needs, without the necessity of treatment by "trial and error". Pharmacogenetics will allow to implement personalized therapy leading to safer and more effective drugs usage. Identification of the individual metabolising paths will reduce patient's exposition to the side effects of many drugs. In spite of many financial and logistic limitations there are chances of introducing the pharmacogenetic analysis -- as an obligatory step -- to the phases II and III of clinical trials by 2020.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Cytochrome P-450 Enzyme System / genetics
  • Drug Therapy / methods*
  • Drug Utilization
  • Humans
  • Pharmacogenetics*

Substances

  • Cytochrome P-450 Enzyme System