RRC ID 82722
Author Sunakawa H, Mizoi K, Takahashi R, Takahashi S, Ogihara T.
Title Impact of P-Glycoprotein-Mediated Drug-Endogenous Substrate Interactions on Androgen and Blood-Brain Barrier Permeability.
Journal J Pharm Sci
Abstract This report focuses on pharmacokinetic drug-endogenous substrate interactions (DEIs). We hypothesized that P-glycoprotein (P-gp)-mediated DEI might affect androgen kinetics, especially its blood-brain barrier (BBB) permeability. The intracellular accumulation of the endogenous substrates of P-gp, testosterone (TES) and androstenedione (ADO) was increased by several tested drugs in uptake studies using P-gp overexpressing cells, indicating that these drugs inhibit P-gp-mediated efflux of TES of ADO from the cells. In a transport study using rat BBB kit, we found that the BBB limited the penetration of TES and ADO into the central nervous system. In addition, tested drugs that cause DEI were found to increase BBB permeability of TES and ADO via P-gp inhibition. In short, this study provides new findings regarding the possibility that DEI may affect the kinetics of endogenous substrates of P-gp.
Volume 113(1)
Pages 228-234
Published 2024-1-1
DOI 10.1016/j.xphs.2023.10.034
PII S0022-3549(23)00440-9
PMID 37898165
MeSH ATP Binding Cassette Transporter, Subfamily B / metabolism ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism Androgens* Animals Biological Transport Blood-Brain Barrier* / metabolism Permeability Rats Testosterone
Resource
Human and Animal Cells LLC-GA5-CoL150(RCB0871)