Pharmacokinetics of DA-8159, a new erectogenic, administered at 10:00 h versus 22:00 h in rats.
Little is known about chronopharmacokinetics of PDE V inhibitors in rats as well as in humans. Hence, the pharmacokinetics of DA-8159 and one of its metabolites, DA-8164, were investigated after intravenous and oral administration of DA-8159 at a dose of 30 mg/kg administered at 10:00 h versus 22:00 h in rats. After intravenous administration of DA-8159 at 22:00 h, the AUC of DA-8159 was significantly greater (528 versus 368 microg min/ml) due to significantly slower CL (56.1 versus 79.5 ml/min/kg) in the rats. After intravenous administration of DA-8159 at 22:00 h, the AUC of DA-8164 was also significantly greater (108 versus 66.8 microg min/ml) possibly due to significantly greater exposure of the parent drug (AUC of DA-8159). After intravenous administration of DA-8164 at 22:00 h, the CL of DA-8164 was significantly slower; hence, this factor could also contribute to the greater AUC of DA-8164 after intravenous administration of DA-8159. However, after oral administration of DA-8159, the AUC values of both DA-8159 and DA-8164 were not significantly different between 10:00 h and 22:00 h. This was not due to decrease in gastrointestinal absorption of DA-8159 at 22:00 h and may be due to changes in intestinal first-pass effect at 22:00 h. The above data suggested that modification of dosage regimen of oral DA-8159 is not necessary in humans between 10:00 h and 22:00 h. Further studies are needed in humans.
Lee
Joo H
JH
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
Kim
Yu C
YC
Kwon
Jong W
JW
Kim
Won B
WB
Lee
Myung G
MG
D000284:Administration, Oral; D000818:Animals; D004334:Drug Administration Schedule; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011743:Pyrimidines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides; D000096926:Benzenesulfonamides
D010726:Phosphodiesterase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C419664:udenafil; D000096926:Benzenesulfonamides