A comparative review of the activity of enzymes of the cytochrome P450 system in humans and laboratory animals. Prognostic value of preclinical models in vivo

Abstract

Cytochrome P450 enzymes play a key role in drug biotransformation. The expression and activity of each CYP450 is influenced by a unique combination of biochemical factors, species and genetic differences, age, sex, nutrition and etc.Cytochromes P450 are a family of heme-containing proteins involved in the metabolism of xenobiotics, drugs, and endogenous compounds. Drugs could act as inducers or inhibitors of cytochrome P450 enzymes. Understanding the mechanisms of inhibition or induction of enzymes is extremely important in preclinical studies and prescribing complex therapy. One of the main challenges in the development of therapeutic agents is to determine which animal species reflects the human ability to metabolize certain drugs. The study of CYPs and their interaction with drugs is an urgent problem in preclinical studies. Thus, an adequate and maximally similar experimental preclinical models are necessary to study the pharmacokinetic and pharmacodynamic properties of promising chemicals and their effect on certain cytochrome P450 enzymes.This review compares the main subfamilies and their enzymes of the cytochrome system of humans and laboratory animals involved in drug metabolism. The problems of choosing biological models in vivo in preclinical studies in the study of medicinal substances are considered. The predictive value of in vivo models of preclinical studies was analyzed from the point of view of the cytochrome P450 system in humans and laboratory animals.