found did not exceed the original level. This indicates that bumetanide is excreted unconjugated in human urine.
However, the urinary excretion of bumetanide m o t be considered as a measure of orally absorbed drug since a Wary excretion of the drug cannot be excluded. Biliary excretion would make the results in accordance with the low dose dog assay, where an almost equal response to the drug was obtained after oral and intravenous administration.
The results confirm the marked saluretic and diuretic effect of bumetanide after oral administration of both 0.5 and 1 mg. to human volunteers and show clearly a parallelism between bumetanide excretion and saluretic action over the total period (Figs. and).
SUMMARY
A GLC determination of bumetanide. using flash-heater methylation by means of a mixture of tetramethylammonium hydroxide and ttimethylanilinium hydroxide, was developed. The flash-heater methylation product of bumetanide proved to be methyl 34N-nbutylanilino)-S-dimethylsulfamyl-4-methoxybenzoate, formed by methylation under simultaneous rearrangement. The GLC detetmination was found to be accurate at concentrations as low as 0.1 mcg./ml. human urine. In six healthy volunteers, the urinary excretion of sodium, potassium, and chloride, the urine volume, and the urinary -very of bumetanide were determined after oral administration of 0.5 and 1 rng. of the drug. A parallelism between bumetanide excretion and saluretic action over the total period of response is shown.