Effects of water deprivation on the pharmacokinetics and pharmacodynamics of bumetanide in rats.

The effects of temporary water deprivation for 48 h on the pharmacokinetics and pharmacodynamics of bumetanide were examined after intravenous (i.v.) administration of bumetanide, 8 mg kg-1 to control and water deprived rats (n = 7). The values of AUC, t1/2 and MRT increased 79.0, 417, and 633 per cent, respectively, and CL and CLNR decreased 44.0 and 41.2 per cent, respectively, in water deprived rats. They were all significantly different. The decreased CLNR in water deprived rats could be due to decreased nonrenal metabolism of bumetanide; it could be supported that the amounts of glucuronide conjugate of bumetanide (52.5 vs 12.9 micrograms), desbutylbumetanide (170 vs 113 micrograms) and its glucuronide conjugation (191 vs 125 micrograms), and sum of the three metabolites (414 vs 229 micrograms), which are expressed in terms of bumetanide excreted in 24 h urine, decreased significantly in water deprived rats. The 8-h urine outputs per 100 g body weight (4.32 vs 1.34 ml) also reduced significantly in water deprived rats, and it might be due to significantly reduced amounts of bumetanide excreted in 8 h urine (90.9 vs 25.7 micrograms) and/or reduced kidney function in water deprived rats. The kidney function based on CLIot (9.87 vs 2.14 ml min-1 kg-1) reduced significantly in water deprived rats. The 8-h urinary excretions of sodium (0.430 vs 0.0818 mmol), potassium (0.567 vs 0.270 mmol), and chloride (0.549 vs 0.0624 mmol) per 100 g body weight also reduced significantly in water deprived rats.