Simvastatin and atorvastatin enhance hypotensive effect of diltiazem in rats

Citation
H. Marumo et al., Simvastatin and atorvastatin enhance hypotensive effect of diltiazem in rats, YAKUGAKU ZA, 121(10), 2001, pp. 761-764
Citations number
21
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN
ISSN journal
0031-6903 → ACNP
Volume
121
Issue
10
Year of publication
2001
Pages
761 - 764
Database
ISI
SICI code
0031-6903(200110)121:10<761:SAAEHE>2.0.ZU;2-0
Abstract
Effects of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in hibitors, simvastatin and atorvastatin, on diltiazem-induced hypotension we re examined in anaesthetized rats and compared to that of pravastatin. Vehi cle, 2 mg/kg/day simvastatin, 2 mg/kg/day atorvastatin, or 4 mg/kg/day prav astatin was administered orally for 4 days. Diltiazem at 3 mg/kg was given orally 2 hours after the final administration of the inhibitors. Arterial b lood pressure was measured via a cannula introduced into the left carotid a rtery, and heart rate was counted from the pulse pressure. In all groups, d iltiazem significantly decreased the mean arterial blood pressure without a ny changes in heart rate. Pretreatment with simvastatin and atorvastatin si gnificantly enhanced the hypotensive effect of diltiazem, while that with p ravastatin did not. Heart rate was not modified by pretreatment with the in hibitors. The results indicate that concomitant use of diltiazem with simva statin or atorvastatin enhances diltiazem-induced hypotension, probably by competitive inhibition of diltiazem metabolism with simvastatin and atorvas tatin metabolisms.