Clinical Pharmacokinetics

, Volume 5, Issue 3, pp 221–245 | Cite as

Clinical Pharmacokinetics of Diuretics

  • Björn Beermann
  • Margaretha Groschinsky-Grind
Article

Abstract

Despite extensive use of diuretics, for only a few have their pharmacokinetics been evaluated.

Bendroflumethiazide is completely absorbed and uptake from the gastrointestinal tract is not changed by food. Plasma half-life is about 3h. Apparent volume of distribution averages 1.5L/kg. Up to two thirds of the drug is eliminated via non-renal routes.

Hydrochlorothiazide is 65% absorbed in healthy fasting subjects and 75% absorbed when given with food. The increased uptake appears to be caused by decreased gastric emptying rate. Absorption is impaired in patients who have undergone intestinal shunt surgery and in some patients with cardiac failure. Plasma half-life averages 10h in subjects with normal renal function. It is prolonged in renal failure as the drug is mainly eliminated via the kidneys in unchanged form.

The bioavailability of hydroflumethiazide is at least 50%. Elimination half-life is about 17h in normal subjects and 10h in patients with cardiac failure. The drug is largely eliminated unchanged in the urine.

The half-life of poly thiazide is approximately 26h. A bout 20% of an oral dose is cleared via the kidneys.

Chlorthalidone is 65% absorbed. Up to 75% of a dose is bound to plasma proteins and extensively to blood cells. Only 1.4% of the total amount of the drug in blood is found in plasma. Plasma half-life averages 40 to 65h. Apparent volume of distribution is close to 300L. This diuretic is mainly eliminated in the urine, although it is metabolised to some extent.

Bumetanide is completely absorbed. Up to 96% is bound to plasma proteins. Apparent volume of distribution ranges from 12 to 35L. Plasma half-life is 1.2 to 1.5h in healthy subjects and does not appear to be prolonged in renal failure. Renal and non-renal clearance contributes equally to its elimination.

The uptake of frusemide (furosemide) from the gastrointestinal tract is about 65% and is decreased in uraemia and nephrosis. Protein binding is 96 to 98% and is diminished in nephrosis. Plasma half-life is approximately 50 minutes in healthy subjects and is prolonged about 3 times in renal failure. Apparent volume of distribution (Vdβ) ranges from 14 to 17L. Urinary excretion and non-renal elimination contribute almost equally to plasma clearance.

The uptake of amiloride is at least 50% and is diminished when given with food. Plasma half-life averages 10h. Amiloride is essentially eliminated unchanged in the urine.

Spironolactone and potassium-canrenoate are both metabolised to canrenone which mainly exerts the renal effects of the drugs. The uptake from the gastrointestinal tract is at least 70 and 100% respectively. The protein binding of canrenone averages 98%. The half-life of canrenone is 18 to 20h after doses of 100 to 400m.g. Canrenone is eliminated as metabolites via the urine and the bile.

Keywords

Clinical Pharmacology Furosemide Hydrochlorothiazide Spironolactone Amiloride 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© ADIS Press Australasia Pty Ltd. 1980

Authors and Affiliations

  • Björn Beermann
    • 1
  • Margaretha Groschinsky-Grind
    • 1
  1. 1.Department of Medicine and Clinical Pharmacology LaboratorySerafimerlasarettetStockholmSweden

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