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Pharmacokinetic changes of DA‐8159, a new erectogenic, after intravenous and oral administration to rats with acute renal failure induced by uranyl nitrate
Author(s) -
Shim Hyun J.,
Kim Yu C.,
Kim Eun J.,
Kim Dong G.,
Kwon Jong W.,
Kim Won B.,
Lee Myung G.
Publication year - 2004
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.389
Subject(s) - uranyl nitrate , pharmacokinetics , chemistry , oral administration , renal function , kidney , medicine , pharmacology , endocrinology , biochemistry , materials science , uranium , metallurgy
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 μg 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 μg 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. Copyright © 2004 John Wiley & Sons, Ltd.