Bumetanide, 2, 8, and 20 mg/kg, was administered both intravenously and orally to determine the pharmacokinetics and pharmacodynamics of bumetanide in rats (n = 10-12). The absorption of bumetanide from various segments of GI tract and the reasons for the appearance of multiple peaks in plasma concentrations of bumetanide after oral administration were also investigated. After i.v. dose, the pharmacokinetic parameters of bumetanide, such as t1/2 (21.4, 53.8 vs. 127 min), CL (35.8, 19.1 vs. 13.4 ml/min per kg), CLNR (35.2, 17.8 vs. 12.6 ml/min per kg) and VSS (392, 250 vs. 274 ml/kg) were dose-dependent at the dose range studied. It may be due to the saturable metabolism of bumetanide in rats. After i.v. dose, 8-hr urine output per 100 g body weight increased significantly with increasing doses and it could be due to significantly increased amounts of bumetanide excreted in 8-hr urine with increasing doses. The total amount of sodium and chloride excreted in 8-hr urine per 100 g body weight also increased significantly after i.v. dose of 8 mg/kg, however, the corresponding values for potassium were dose-independent. After oral administration, the percentages of the dose excreted in 24-hr urine as unchanged bumetanide were dose-independent. Bumetanide was absorbed from all regions of GI tract studied and approximately 43.7, 50.0, and 38.4% of the orally administered dose were absorbed between 1 and 24 hr after oral doses of 2, 8, and 20 mg/kg, respectively. Therefore, the appearance of multiple peaks after oral administration could be mainly due to the gastric emptying patterns.(ABSTRACT TRUNCATED AT 250 WORDS)