Negligible pharmacokinetic interaction between oral DA‐8159, a new erectogenic, and amlodipine in rats

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 AUC0−6 h of amlodipine was significantly greater than the controls (34.5±6.01 compared with 28.0±4.70 µg 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. Copyright © 2006 John Wiley & Sons, Ltd.

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