Dose dependency of furosemide-induced sodium excretion

Intravenous furosemide doses ranging from 5 to 120 mg were given to healthy young volunteers with and without individualized active rehydration with a sodium chloride solution. Sodium excretion rates and fractional sodium excretions (FENa) percentages were correlated significantly with dose and with urinary excretion rates of furosemide. The ED50 was below 5 mg and no additional natriuretic effect was seen above 40 mg. The efficiency (FENa percentage per microgram of furosemide excreted per minute during a certain clearance period) was dependent on hydration and on time. For the period 15 to 30 min a significant linear relationship between furosemide dose and the reciprocal of the efficiency indicated a higher efficiency for lower doses and a theoretical maximal value of FENa of 0.4% per micrograms of furosemide excreted per minute. A relative value for a dose-dependent efficiency reduction was calculated for each dose. The ED50 for dose-dependent efficiency reduction was about 12 mg i.v. Simultaneous measurements of lithium clearance indicated a proximal site of action for furosemide which was saturated at furosemide excretion rates above 50 micrograms/minute. For the major, distal, site of action no maximal value was demonstrated. It is concluded that a wanted balance between a strong natriuretic effect and weak sodium retaining mechanism not necessarily is achieved by a high dose and that information concerning that problem must be obtained from studies in relevant patient groups.