Pharmacokinetic and pharmacodynamic changes of azosemide after intravenous and oral administration of azosemide to uranyl nitrate-induced acute renal failure rats

✍ Scribed by Kwang J. Park; Woo H. Yoon; Sung H. Kim; Wan G. Shin; Myung G. Lee

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 144 KB
• Volume: 19
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199804)19:3<141::aid-bdd119>3.0.co;2-3

✦ Synopsis

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 mg 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 mg 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 B0.098) 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.