Clinical pharmacokinetics of some newer diuretics.
Several new diuretics have recently been developed. This review summarises the published knowledge about some of them. Azosemide is a loop diuretic. The bioavailability is about 15% and it has a half-life of 2 to 3 hours. Renal and non-renal clearance are 1.32 and 5.4 L/h, respectively. Etozolin is also a loop diuretic. It is rapidly metabolised to the active metabolite, ozolinone. The gastrointestinal uptake of etozolin is almost complete. The plasma half-life of etozolin and ozolinone are 2 and 10 hours, respectively. The compounds are mainly eliminated as metabolites. Renal and liver impairment do not seem to change the pharmacokinetics. Fenquizone has properties similar to the thiazides. The plasma half-life is approximately 17 hours. Apparent volume of distribution averaged 686 L and renal clearance is 7.2 L/h. Indapamide acts predominantly on the proximal segment of the distal tubule and also has direct vasodilatory effects. Gastrointestinal uptake is at least 80%. The drug binds highly to carbonic anhydrases of red blood cells. Protein binding is about 80%, while terminal plasma half-life is 15 hours and the apparent volume of distribution 25 L. Renal clearance is 0.3 L/h and non-renal clearance 0.9 L/h. Several metabolites have been described, of which one major metabolite is pharmacologically active. Muzolimine is a loop diuretic. Its uptake is almost complete, but decreased substantially by food. The protein binding is about 65%, the apparent volume of distribution is about 1 L/kg and average terminal half-life 10 to 20 hours. Elimination is mainly non-renal, and non-renal clearance ranges between 0.5 and 1.32 L/h. The pharmacokinetics of the drug do not seem to be changed in cardiac failure. Terminal plasma half-life is essentially unchanged in patients with renal failure, except in those with very severe reduction of glomerular filtration rate. Piretanide is a loop diuretic which is about 6 times as potent as frusemide (furosemide). Its bioavailability is most likely complete in healthy subjects and in renal patients. Protein binding in healthy subjects is about 95%. The plasma half-life of the drug is about 1 hour and apparent volume of distribution averages about 17 L. Renal and non-renal clearance are about 6 L/h, although renal clearance is decreased in renal failure: this decrease is correlated with glomerular filtration rate. Non-renal clearance is unchanged in renal failure, as is the apparent volume of distribution.(ABSTRACT TRUNCATED AT 400 WORDS)
Beermann
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B
Section of Cardiology, Karolinska Institute at Huddinge Hospital.
Grind
M
M
D004232:Diuretics / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans
D004232:Diuretics