Comparison of diuretic effects and pharmacokinetics of torasemide and furosemide after a single oral dose in patients with hydropically decompensated cirrhosis of the liver.
In a controlled double-blind randomized clinical trial, the pharmacodynamics and pharmacokinetics of 20 mg torasemide (1-isopropyl-3-([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea) (n = 10) and 40 mg furosemide (n = 9) were compared over 24 h after single oral administration to patients with ascites due to cirrhosis of the liver. The overall 24-h excretion of volume and sodium was not significantly different between patients receiving torasemide or furosemide. The diuretic effect of torasemide, however, was longer in duration than that of furosemide. This was in accordance with the pharmacokinetic behaviour of torasemide and furosemide. The serum elimination half-life of torasemide was longer (4.8 h) than that of furosemide (2.2 h) in these patients and also longer than that in healthy volunteers (3 h). The areas under the serum concentration-time curves for torasemide were higher than in healthy subjects by a factor of 2.5. In parallel with the considerably delayed formation of the diuretically inactive metabolite M5, which is formed via the diuretically active metabolite M1, the serum concentration of M1 was increased in these patients. However, the overall excretion of torasemide and the different metabolites was similar compared to healthy volunteers. These results indicate that the pharmacokinetics and metabolism of torasemide depend on liver function. No adverse reaction were experienced in either group.
Brunner
G
G
Medizinische Hochschule, Oststadt Krankenhaus, Hannover, Fed. Rep. of Germany.
von Bergmann
K
K
Häcker
W
W
von Möllendorff
E
E
D000284:Administration, Oral; D001835:Body Weight / Q000187:drug effects; D002986:Clinical Trials as Topic; D004231:Diuresis / Q000187:drug effects*; D004232:Diuretics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005665:Furosemide / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011897:Random Allocation; D013056:Spectrophotometry, Ultraviolet; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077786:Torsemide
D004232:Diuretics; D013449:Sulfonamides; D005665:Furosemide; D000077786:Torsemide