The effects of piretanide on catecholamine metabolism, plasma renin activity and plasma aldosterone: a double-blind study versus furosemide in healthy volunteers

Abstract

In a double-blind, crossover study, 8 male volunteers (mean age: 25.9 years) received successively 6 different regimens of two diuretics, piretanide and furosemide, with a 1-week wash-out period between each drug regimen. Piretanide (6 mg) or furosemide (40 mg) were given either once daily at 08.00 hours or twice daily at 08.00 and 12.00 hours or at 08.00 and 20.00 hours. Each of these phases lasted for 1 week. Serial measurements were performed on plasma renin activity, plasma aldosterone, plasma adrenaline, plasma noradrenaline, plasma dopamine, cumulative urinary excretion of aldosterone, urine volume and urine osmolality. Plasma catecholamines showed no clinically relevant changes during all three regimens of piretanide or furosemide dosage. Piretanide and furosemide both induced a short-term increase in plasma renin activity with a maximum about 4 hours after dosing which returned to initial levels after approximately 12 hours regardless of whether a single or twice daily dose had been given. After 1 week of piretanide given once daily, lower plasma renin activity was found than after furosemide. Furosemide given once daily caused higher plasma aldosterone concentrations than did piretanide. The lowest plasma aldosterone concentrations were found during the twice-daily piretanide regimen at 08.00 and 20.00 hours. Aldosterone excretion in urine was also higher during furosemide than during piretanide administration. Piretanide given twice daily at both 08.00 and 12.00 hours or 08.00 and 20.00 hours caused the most insignificant changes in aldosterone excretion. It is suggested that piretanide, in comparison to furosemide, activates the counter-regulatory mechanisms, which may diminish the antihypertensive effect of the diuretic, to a much lesser extent.