Pharmacokinetic changes of DA‐8159, a new erectogenic, and one of its metabolites, DA‐8164 after intravenous and oral administration of DA‐8159 to spontaneously hypertensive rats and DOCA–salt‐induced hypertensive rats

The pharmacokinetics of DA‐8159 and one of its metabolites, DA‐8164, were compared after intravenous and oral administration of DA‐8159 at a dose of 30 mg/kg to spontaneously hypertensive rats (SHRs) at 16 and 6 weeks old and their respective age‐matched control normotensive Kyoto–Wistar rats (KW rats), and deoxycorticosterone acetate–salt‐induced hypertensive rats (DOCA–salt rats) at 16 weeks old and their age‐matched control Sprague–Dawley rats. After oral administration of DA‐8159 to 16‐week‐old SHRs, the AUC values of both DA‐8159 (157 versus 103 µg min/ml) and DA‐8164 (215 versus 141 µg min/ml) were significantly greater, but the values of DA‐8159 were reversed in 16‐week‐old DOCA–salt rats (125 versus 200 µg min/ml). However, the AUC values of both DA‐8159 and DA‐8164 were not significantly different between the 6‐week‐old SHRs and their control rats. The above AUC differences in 16‐week‐old SHRs may be due to neither hereditary characteristics of SHRs nor the hypertensive state itself. Copyright © 2005 John Wiley & Sons, Ltd.