A comparison of the pharmacokinetics and diuretic effects of two loop diuretics, torasemide and furosemide, in normal volunteers

Summary

The diuretic effects of torasemide and furosemide at three different steady-state plasma and urinary drug levels were compared in a randomized cross-over study in 6 healthy volunteers. Each trial with either torasemide or furosemide consisted of four consecutive periods of 90 min, the first being a control period, and during the three other periods, increasing doses of drug were administered. Each 90-min period was itself divided into three 30 min blood sampling and urinary collection periods. The urinary losses of water and electrolytes were compensated within each 30-min period by intravenous infusion of saline (NaCl) and 5% glucose solutions, to which KCl was added. A constant dose of calcium gluconate was given to compensate, at least in part, any calcium loss.

Data from each 30 min control and the 3 drug dose periods, corresponding to full steady-state conditions, were used for clearance determinations and measurement of plasma and urinary drug concentrations.

Urine volume, osmolar clearance, absolute and fractional urinary excretion of sodium, potassium, chloride, calcium and magnesium and creatinine clearance increased similarly after torasemide and furosemide according to the logarithm of the dose of the drug. Free water clearance stabilized at a constant level with torasemide and increased continuously after each dose of furosemide. During each of the three drug administration periods, the plasma levels of torasemide were not significantly different from those of furosemide, whereas the urinary concentrations and absolute excretion rates of torasemide were more than 5-times lower than those of furosemide.

The urinary concentrations and excretion rates of both drugs were significantly correlated with their effect on urinary volume (p<0.05).

It is concluded that torasemide is a potent loop diuretic. It acts at lower urinary levels than furosemide. This might indicate more effective binding of torasemide to luminal tubular receptors or an additional effect of this drug on non-luminal receptors.