Clinical Pharmacokinetics of Diuretics

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 1.5£/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 hal/-life is about 17h in normal subjects and IOh in patients with cardiac failure. The drug is largely eliminated unchanged, in the urine. The half-life of poly thiazide is approximately 26h. About 20 % of an oral dose is cleared via the kidneys. Chlorthalidone is 65 % absorbed. Up to 75 % of a dose is bound to'plasmaproteins and extensively to blood cells. Only 1.4 % of the tota'i amount of the drug in blood is found in plasma.' Plasma half-life averages 40 to 65h. Apparent volume of distribution is close to 300£. 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 35£. Plasma hal/-life is 1.2 to J .5h in healthy subjects and does not appear to be prolonged in renal failure. Renal and non-renal clearance contributes equalfY 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 renalfailure. Apparent volumeo/distribution (Vd~rangesfrqm J4 to 11£. Urinary excretion and non-renal elimination contribute almost equally to plasma clearance. The uptake of/ §...mi/ori~is at least 50 % and is diminished when given with food. Plasma half-life averages IOh. Amiloride is essentially eliminated unchanged in'the urine. '

Does Smoking Act as a Friend or Enemy of Blood Pressure? Let Release Pandora's Box

“…Diuretics are a complex class of drugs largely used for the treatment of hypertension [71, 72]. With the exception of the antagonists of aldosterone, the main mechanism of action of these drugs consists of inhibiting ion transporters in the luminal membrane of the renal tubule.…”

Diuretic Resistance: Mechanisms and Therapeutic Strategies

“…In addition, there is no evidence of reabsorption of loop diuretics from the nephron. Thus, vir tually all of the diuretic that reaches the urine does so by active secretion via the organic acid secretory pump of the proximal tubule of the nephron [1,4,5], In summary, examining the pharmacoki netic determinants of resistance to a diuretic requires assessment of whether or not the dis ease process affects the circulating concentra tion of the diuretic and whether its renal clear ance is changed. For example, a change in bio availability caused by the disease process could affect serum concentrations.…”

“…Because both non-renal and renal clearance of furosemide are diminished in patients with severe renal insufficiency, total clearance is dramatically decreased resulting in a several fold prolongation in the half-life of elimina tion (table 3) [1,4,5], In contrast, the main tained non-renal clearance of bumetanide and torasemide results in only minimal (bu metanide) or negligible (torasemide) changes in total clearance, so that the elimination halflives of these two loop diuretics are essentially unchanged in patients with severe renal dis ease compared with subjects with normal re nal function [3,21], From these data, it is possible to predict a ceiling dose for various loop diuretics in pa tients with severe renal insufficiency (table 3). The intravenous doses of loop diuretics that are required to reach maximal response in patients with normal renal function are: furo semide, 40 mg; bumetanide, 1 mg; and tora semide, 15-20 mg [1,3].…”

Determination and characterization of diuretics in human urine by liquid chromatography coupled to pneumatically assisted electrospray ionization mass spectrometry

“…Although some diuretics are extensively metabolized (e.g. spironolactone, excreted in urine as canrenone and other metabolic products),3, 4 most of them are excreted unchanged in urine to variable extents 5. Liquid chromatographic/ultraviolet (LC/UV) methods have been described for the determination of these compounds, most of them involving acetonitrile–water mixtures as mobile phases 6–8.…”