PECULIARITIES OF INTERACTION OF AZOLE-CONTAINING DRUGS AND PESTICIDES WITH CYP2C9 POLYMORPHIC ISOFORMS

Abstract

Azole-containing compounds are often co-administrated with different classes of medications, and are widely used as pesticides in agriculture. Besides the main action, azole-containing compounds can directly affect the human cytochrome P450 system, inhibiting the human CYP catalytic activity, and thereby leading to metabolism disturbances and the elimination of other drugs, causing the toxic effect or resulting in a complete absence of the effect of the drug used. In the context of polypharmacy, it is important to take into account the influence of the genetic polymorphism of CYP2C9 both on the metabolism of individual drugs and on drug-drug interactions. In this paper, a comprehensive comparative study was conducted to assess the binding of various pesticides and antifungal drugs to the active center of CYP2C9*1, CYP2C9*2, CYP2C9*3. We have shown significant differences in the azole affinity to CYP2C9*1, CYP2C9*2, and CYP2C9*3. The obtained findings allow us to predict drug-drug interactions, as well as changes in the metabolism of drugs in the presence of specific xenobiotics.