Effect of Chloral Hydrate on Renal Excretion of Furosemide in Rabbits

Abstract

The mechanism of interaction of furosemide (FS) with chloral hydrate (CH) was investigated in rabbits. The co-administration of CH markedly enhanced the plasma concentration of FS, and reduced the amount of cumulative urinary excretion of FS after intravenous bolus injection. Furthermore, the co-administration of CH was found to significantly decrease the renal clearance (Cl_r) of FS, but to have no effect on its extrarenal clearance (Cl_nr). These clearly indicate that the interaction of FS with CH is generated during renal excretion. Interestingly, the co-administration of CH reduced the amount of cumulative urinary excretion of phenolsulfonphthalein, which is excreted exclusively by tubular secretion, whereas it did not affect the amount of cumulative urinary excretion of inulin, which is excreted exclusively by glomerular filtration. The co-administration of CH caused no change in urinary pH after intravenous bolus injection of FS. These findings suggest that the co-administration of CH may depress the renal excretion of FS by inhibiting the tubular secretion.