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Pharmacokinetic and pharmacodynamic changes of azosemide after intravenous and oral administration of azosemide to uranyl nitrate‐induced acute renal failure rats
Author(s) -
Park Kwang J.,
Yoon Woo H.,
Kim Sung H.,
Shin Wan G.,
Lee Myung G.
Publication year - 1998
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/(sici)1099-081x(199804)19:3<141::aid-bdd119>3.0.co;2-3
Subject(s) - pharmacokinetics , uranyl nitrate , pharmacology , chemistry , oral administration , renal function , pharmacodynamics , excretion , medicine , endocrinology , materials science , uranium , metallurgy
The pharmacokinetic and pharmacodynamic differences of azosemide were investigated after intravenous (IV) and oral administration of azosemide, 10 mg kg −1 , to the control and uranyl nitrate‐induced acute renal failure (U‐ARF) rats. After IV administration, the plasma concentrations of azosemide were significantly higher in the U‐ARF rats and this resulted in a significant increase in AUC (2520 versus 3680 μg min mL −1 ) and significant decrease in Cl (3.96 versus 2.72 mL min −1 kg −1 ) of azosemide. The significant decrease in Cl in the U‐ARF rats was due to the significant decrease in Cl r of azosemide (1.55 versus 0.00913 mL min −1 kg −1 ) due to the decrease in kidney function in the U‐ARF rats. After IV administration, the urine output (38.5 versus 8.45 mL 100 g −1 body weight) and urinary excretion of sodium (4.60 versus 0.420 mmol 100 g −1 body weight) decreased significantly in the U‐ARF rats. After oral administration, the AUC 0–8 h of azosemide decreased significantly (215 versus 135 μg min mL −1 ) in the U‐ARF rats possibly due to the decreased GI absorption of azosemide. After oral administration, the 24‐h urine output decreased considerably (16.1 versus 11.2 mL 100 g −1 body weight, p <0.098) and the 24‐h urinary excretion of sodium (1.74 versus 0.777 mmol 100 g −1 body weight) decreased significantly in the U‐ARF rats. The IV and oral doses of azosemide needed to be modified in the acute renal failure patients if the present rat data could be extrapolated to humans. © 1998 John Wiley & Sons, Ltd.