Pharmacokinetic changes of DA-8159, a new erectogenic, after intravenous and oral administration to rats with diabetes mellitus induced by streptozotocin.
Intravenous administration of DA-8159, 30 mg/kg, to rats with diabetes mellitus induced by streptozotocin (DMIS), AUC of DA-8164 (a metabolite) was significantly smaller in rats with DMIS (57.9 compared with 81.8 microg x min/mL). This may be due to more contribution of significantly faster clearance of DA-8164 than that of significantly greater formation of DA-8164 in the rats. For example, the CL of DA-8164 was significantly faster (9.68 compared with 6.29 mL/min/kg) after intravenous administration of DA-8164, 10 mg/kg, to rats with DMIS and in vitro intrinsic clearance for the formation of DA-8164 was significantly faster (1.92 compared with 1.59 microL/min/mg protein) in hepatic microsomal fraction of rats with DMIS due to significant increase in expression of CYP3A1(23) in the rats. DA-8164 was formed mainly via CYP3A1/2 in rats. After intravenous administration of DA-8159, renal clearance was significantly faster in rats with DMIS (5.79 compared with 2.80 mL/min/kg) due to urine flow-dependent renal clearance of DA-8159 in rats. After oral administration of DA-8159, the AUC values of both DA-8159 and DA-8164 were not significantly different between two groups of rats. Although the exact reason is not known it may be due to changes in first-pass effect of DA-8159 in rats with DMIS.
Kim
Yu C
YC
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
Kwon
Jong W
JW
Kim
Won B
WB
Lee
Inchul
I
Lee
Myung G
MG
D000284:Administration, Oral; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D011743:Pyrimidines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides; D000096926:Benzenesulfonamides
D011743:Pyrimidines; D013449:Sulfonamides; C419664:udenafil; D000096926:Benzenesulfonamides