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) |