Gender-related differences in drug effects: The role of multidrug resistance proteins

Mechanisms of the involvement of multidrug resistance proteins (MRPs) in the formation of gender-related differences in drug effectiveness and adverse effects have been analyzed. The structure, tissue and cellular localization, substrate specificity, and functions of MRPs are discussed. The regulation of MRP expression and activity by endogenous metabolites, signaling compounds, including sex hormones, and pharmaceutical agents is described. Nuclear receptors have been shown to play a role in the regulation of MRP expression. Data on gender-related differences in the expression of MRPs and nuclear receptors that are involved in the induction of MRPs in the liver and kidney are presented. It is concluded that gender-related differences in the expression and functional activity of MRPs in excretory organs (the liver and kidney) may significantly contribute to gender dependence of drug pharmacokinetics and effectiveness.