[Epigenetic Regulation of Pharmacokinetic-related Genes in Human Tissues].

[Epigenetic Regulation of Pharmacokinetic-related Genes in Human Tissues]. Yakugaku Zasshi. 2018;138(11):1391-1396 Authors: Hirota T Abstract The translocation of drugs across biological membranes not only occurs via passive diffusion but also by transporter-mediated processes. Knowledge of tissue-specific drug transporter expression, as well as characterization of substrate drugs of individual transporters, leads to a better understanding of the role of these transporters in the pharmacokinetics of drugs. The ATP-binding cassette transporter family member breast cancer resistance protein (BCRP) is one of the most important intestinal efflux transporters involved in the intestinal absorption or permeability of drugs. A genetic variant in the BCRP, 421C>A, is a useful biomarker for explaining large interindividual differences in the pharmacokinetics of sulfasalazine (SASP), a BCRP substrate. However, large intragenotypic differences remain in spite of the incorporation of this genotype into the pharmacokinetics of SASP. Epigenetic regulation alters gene expression without changing DNA sequences. In epigenetic regulation, microRNAs (miRNAs) appear to be the most extensively investigated due to their important roles in the posttranscriptional regulation of mRNAs. Our study showed that miR-328 negatively regulates BCRP expression in human tissues, and the intestine-derived exosomal miR-328 levels positively correlated with the SASP ar...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research