PMID: 24366438Dec 25, 2013Paper

Role of P-glycoprotein in regulating cilnidipine distribution to intact and ischemic brain

Drug Metabolism and Pharmacokinetics
Kentaro YanoTakuo Ogihara

Abstract

Cilnidipine is reported to show antihypertensive and neuroprotective actions in a rat brain ischemia model, but is barely distributed to normal brain, suggesting that its uptake into normal brain is inhibited by efflux transporter(s), such as P-glycoprotein (P-gp). Here, we investigated whether P-gp regulates the brain distribution of cilnidipine. Intracellular accumulation of cilnidipine was decreased in P-gp-overexpressing porcine kidney epithelial cells (LLC-GA5-COL150 cells) compared with control LLC-PK1 cells and the decrease was markedly inhibited by verapamil, a P-gp inhibitor. Further, cilnidipine concentration in the brain of P-gp knockout mice was significantly increased after cilnidipine administration, compared with that in wild-type mice. Moreover, when cilnidipine was administered to male spontaneously hypertensive rats (SHR) with tandem occlusion of the distal middle cerebral and ipsilateral common carotid artery, its concentration in the ischemic hemisphere was 1.6-fold higher than that in the contralateral hemisphere. This result was supported by visualization of cilnidipine distribution using matrix-assisted laser desorption/ionization-time of flight/mass spectrometry (MALDI-TOF/MS) imaging. Our results indica...Continue Reading

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Citations

Nov 13, 2015·Expert Review of Proteomics·Marta Martin-LorenzoFernando Vivanco
Feb 19, 2016·The Journal of Pharmacy and Pharmacology·Kentaro YanoTakuo Ogihara
Feb 18, 2017·Clinical Pharmacokinetics·Anton IvanyukThierry Buclin
Jan 10, 2018·Biological & Pharmaceutical Bulletin·Kentaro YanoTakuo Ogihara
Jun 22, 2017·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·I V ChernykhN M Popova
Apr 23, 2020·Pharmacology & Therapeutics·Eva Gil-MartinsRenata Silva

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