Abstract
A pharmacokinetic interaction between oral DA-8159 and amlodipine was evaluated in male Sprague-Dawley rats. In rats pretreated with troleandomycin (a main inhibitor of CYP3A1/2 in rats), the AUC(0-6 h) of amlodipine was significantly greater than the controls (34.5+/-6.01 compared with 28.0+/-4.70 microg min/ml), indicating that amlodipine is metabolized via CYP3A1/2 in rats. It was reported that the metabolism of DA-8159 and the formation of DA-8164 (a metabolite of DA-8159) were mainly mediated via CYP3A1/2 in rats, and amlodipine significantly inhibited the CYP3A2 in rats. Therefore, a pharmacokinetic interaction between the two drugs could be expected. However, after oral administration of DA-8159 at a dose of 30 mg/kg with or without oral amlodipine at a dose of 5 mg/kg to rats, the pharmacokinetic parameters of DA-8159 and DA-8164 were not significantly different between the two groups of rats. Similar results were also obtained from amlodipine between with and without DA-8159. The above data indicated that the pharmacokinetic interaction between oral DA-8159 and amlodipine was almost negligible in rats.
2006 John Wiley & Sons, Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Amlodipine / administration & dosage
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Amlodipine / blood
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Amlodipine / pharmacokinetics*
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Animals
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Area Under Curve
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Aryl Hydrocarbon Hydroxylases / metabolism
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Chromatography, High Pressure Liquid
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Cytochrome P-450 CYP3A
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Drug Interactions
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / pharmacokinetics
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Feces / chemistry
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Gastrointestinal Tract / metabolism
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Injections, Intraperitoneal
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Injections, Intravenous
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Male
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Penile Erection / drug effects*
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Penile Erection / physiology
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Phosphodiesterase Inhibitors / administration & dosage
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Phosphodiesterase Inhibitors / blood
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Phosphodiesterase Inhibitors / pharmacokinetics
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Pyrimidines / administration & dosage
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Pyrimidines / metabolism
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Pyrimidines / pharmacokinetics*
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Rats
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Rats, Sprague-Dawley
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Sulfonamides
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Time Factors
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Troleandomycin / administration & dosage
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Troleandomycin / pharmacokinetics
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Tyrosine / administration & dosage
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Tyrosine / analogs & derivatives
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Tyrosine / pharmacokinetics
Substances
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DA-8164
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Enzyme Inhibitors
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Phosphodiesterase Inhibitors
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Pyrimidines
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Sulfonamides
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Amlodipine
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Tyrosine
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Troleandomycin
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Aryl Hydrocarbon Hydroxylases
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Cyp3a23-3a1 protein, rat
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Cytochrome P-450 CYP3A
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udenafil
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tiropramide