Acute and chronic effects of torasemide in healthy volunteers

The acute and chronic effects of torasemide (1-isopropyl-3- ([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea) were investigated in 2 separate groups of healthy volunteers: 1. In a first group of 6 volunteers, the acute effects of torasemide were investigated at 3 different steady state plasma and urinary drug levels and compared to those of furosemide according to a randomized cross-over design. Each drug was continuously given by i.v. route in 3 consecutive periods of 90 min immediately after a control run-in period of 90 min. The last 30 min period of each control and 3 drug administration periods fulfilled the steady state conditions and were used for clearance determinations and plasma and urinary concentrations of drug. The plasma levels of both torasemide and furosemide increased progressively at increasing plateaus during each of the 3 drug periods with no significant difference between each of the 2 drugs. However, the urinary drug excretions were 5 times lower with torasemide than with furosemide. In spite of these highly different urinary drug concentrations, torasemide and furosemide induced a similar increase of the water excretion, osmolar and creatinine clearances and absolute and fractional excretions of sodium, potassium, chloride, calcium and magnesium. The correlation between the logarithm of the drug doses and the urinary effects were highly significant with both drugs. Free water clearance was stable throughout the torasemide administration, whereas it increased steadily with each dose of furosemide. The fractional distal chloride reabsorption decreased significantly more with torasemide than with furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)