Pharmacokinetic changes of DA-8159, a new erectogenic, after intravenous and oral administration to rats with acute renal failure induced by uranyl nitrate.
The pharmacokinetic parameters of DA-8159, a new erectogenic, were compared after intravenous and oral administration of the drug at a dose of 30 mg/kg to control rats and rats with acute renal failure induced by uranyl nitrate (U-ARF). After intravenous administration to rats with U-ARF, the plasma concentrations of DA-8159 were higher than those in control rats. This resulted in a significantly greater area under the plasma concentration-time curve from time zero to time infinity (AUC) of DA-8159 in rats with U-ARF (304 compared with 365 microg min/ml for control rats and rats with U-ARF). The significantly greater AUC in rats with U-ARF was due to significantly slower total body clearance (Cl) of DA-8159 (98.6 compared with 82.2 ml/min/kg). The significantly slower Cl in rats with U-ARF was due to slower renal clearance (1.07 ml/min/kg compared with not calculable, due to impaired kidney function) and nonrenal clearance (97.5 compared with 82.2 ml/min/kg due to slower metabolism) than those in control rats. After oral administration of DA-8159 to rats with U-ARF, the AUC (122 compared with 172 microg min/ml) was significantly greater and Cl(R) was slower (3.47 ml/min/kg compared with not calculable) than those in control rats. The significantly greater AUC in rats with U-ARF could be due to slower Cl of DA-8159 in the rats.
Shim
Hyun J
HJ
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, Republic of Korea.
Kim
Yu C
YC
Kim
Eun J
EJ
Kim
Dong G
DG
Kwon
Jong W
JW
Kim
Won B
WB
Lee
Myung G
MG
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004355:Drug Stability; D007172:Erectile Dysfunction / Q000188:drug therapy; D007275:Injections, Intravenous; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides; D013997:Time Factors; D014502:Uranyl Nitrate; D000096926:Benzenesulfonamides
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases; D011743:Pyrimidines; D013449:Sulfonamides; D014502:Uranyl Nitrate; C517384:Pde5a protein, rat; C419664:udenafil; D000096926:Benzenesulfonamides