Pharmacodynamics and pharmacokinetics of furosemide combinations with potassium-retaining and thiazide-like diuretics: Clearance and micropuncture studies

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Abstract
The interaction between furosemide on the one hand and hydrochlorothiazide, tizolemide, amiloride and triamterene on the other was studied by clearance and micropuncture techniques in rats. Simultaneous administration of furosemide with hydrochlorothiazide and tizolemide distinctly increased the natriuresis compared to that induced by furosemide alone, whereas the potassium excretion diminished. In contrast, amiloride and triamterene primarily decreased furosemide-induced fractional potassium excretion by about 30%, whereas sodium excretion increased only slightly compared to that produced by furosemide alone. Hydrochlorothiazide and triamterene significantly decreased furosemide secretion and changed its pharmacokinetics. Furosemide plasma concentration increased, thus possibly prolonging the salidiuretic effect. Amiloride and tizolemide did not influence the secretion of furosemide at all.