Pharmacokinetic and pharmacodynamic changes of azosemide after intravenous and oral administration of azosemide to uranyl nitrate-induced acute renal failure rats.
The pharmacokinetic and pharmacodynamic differences of azosemide were investigated after intravenous (i.v.) 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 micrograms 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 Clr 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 AUC0-8 h of azosemide decreased significantly (215 versus 135 micrograms 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 i.v. 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.
Park
K J
KJ
College of Pharmacy, Seoul National University, Shinlim-Dong, Kwanak-Gu, Republic of Korea.
Yoon
W H
WH
Kim
S H
SH
Shin
W G
WG
Lee
M G
MG
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D001659:Biliary Tract / Q000378:metabolism; D004064:Digestive System / Q000378:metabolism; D004195:Disease Models, Animal; D004232:Diuretics / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013424:Sulfanilamides / Q000097:blood / Q000493:pharmacokinetics*; D014502:Uranyl Nitrate; D013777:Tetrazoles; D013876:Thiophenes; D000096926:Benzenesulfonamides
D004232:Diuretics; D013424:Sulfanilamides; D014502:Uranyl Nitrate; C018222:azosemide; D013777:Tetrazoles; D013876:Thiophenes; D000096926:Benzenesulfonamides