Renal Excretory Actions of Furosemide, of Hydrochlorothiazide and of the Vasodilator Flosequinan in Healthy Subjects

Abstract

The responses of urine and urinary solute outputs and flows to single doses of 80 mg furosemide, 25 mg hydrochlorothiazide, and 100 or 200 mg flosequinan were investigated in healthy subjects using a double-blind, randomized, crossover design. Treatment days were separated by 7 days. Volumes of urine passed between 0 and 3, 3 and 6, 6 and 9, 9 and 12, and 12 and 24 h after drug administration were determined and urinary concentrations of chloride, sodium, potassium, calcium, magnesium, phosphate, zinc, urate, urea and creatinine were measured. Venous blood was taken before and 6 and 24 h after dosing and the serum was analysed for the same solutes as urine. Excretions of urine and urinary solutes accumulated at the end of each collection period after each formulation were fitted by the UY function, whose derivative provided corresponding flows as functions of time. Instantaneous renal clearances of solutes 6 and 24 h after dosing were evaluated from the flows. This approach showed that 80 mg furosemide and 25 mg hydrochlorothiazide were equipotent 24-h natriuretics. Rapid urinary responses which then rebounded compared with the control responses were produced by 80 mg furosemide, whereas changes after 25 mg hydrochlorothiazide were smooth. Neither 100 or 200 mg flosequinan showed any important effect on urinary excretion.

Serum zinc values in children with congenital heart disease

“…The difference did not reach statistical significance. This is consistent with some studies that did not show any significant difference in the serum zinc level of volunteers on frusemide and hydrochlorthiazide 12,20 . However, the serum zinc levels of children with congestive heart failure was found to be significantly lower than their age and sex matched controls in a study by Atlihan and co-workers 20 .…”

“…The diuretic therapy in patients with heart failure causes zincuria 11 . The thiazide and angiotensin converting enzyme inhibitors are more likely to cause zincuria than other medicines used for CHF 12,13 . In resource poor countries, because the capacity for surgical interventions for children with CHD is limited, most of these children live with chronic heart failure and the recurrent bronchopneumonia which may predispose them to zinc depletion.…”

Zinc balance and medications commonly used in the management of heart failure

“…In healthy volunteers, administration of a single oral dose of 25 mg hydrochlorothiazide or 80 mg furosemide, compared to placebo and a combination of 12.5 mg hydrochlorothiazide with 200 mg acebutolol (beta-blocker), did not change serum and total 24-hour urinary zinc excretion [18,19]. However, in hypertensive patients, treatment with hydrochlorothiazide, bendroflumethiazide or chlorthalidone for two weeks resulted in an increase of urinary zinc concentration by 30% and the 24-hour zinc excretion by 60% [20].…”

“…Moreover, poor growth and reduction of food intake were also observed [27]. However, in contrast, in human studies a single oral dose of furosemide in healthy volunteers did not alter serum and 24-hour urinary zinc excretion [18] and in patients with moderate HF treated with a single dose of furosemide in the form of tablets or solution, no change in serum zinc (or 24-hour urinary zinc excretion), sodium, potassium, calcium, or magnesium was observed [28].…”

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“…Earlier studies (see [1]) used large doses, collected urine for varying times post-dosing and were poorly controlled. However, in a series of double-blind, random order, placebo controlled studies, Reyes and colleagues [77][78][79][80] showed statistically significant increases over basal Mgu for hydrochlorothiazide, chlorthalidone and frusemide. There was no evidence of a dose-response relationship and spontaneous variation from day to day was not assessed.…”