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 microg min/ml) and DA-8164 (215 versus 141 microg min/ml) were significantly greater, but the values of DA-8159 were reversed in 16-week-old DOCA-salt rats (125 versus 200 microg 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.
Kim
Yu C
YC
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Republic of Korea.
Shim
Hyun J
HJ
Lee
Joo H
JH
Kim
Dong S
DS
Kwon
Jong W
JW
Kim
Won B
WB
Lee
Inchul
I
Lee
Myung G
MG
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003900:Desoxycorticosterone; D006207:Half-Life; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010879:Piperazines / Q000493:pharmacokinetics; D011687:Purines; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D012965:Sodium Chloride; D013449:Sulfonamides; D013450:Sulfones; D000096926:Benzenesulfonamides
D003900:Desoxycorticosterone; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D011743:Pyrimidines; D000068677:Sildenafil Citrate; D012965:Sodium Chloride; D013449:Sulfonamides; D013450:Sulfones; C419664:udenafil; D000096926:Benzenesulfonamides