FUROSEMIDE PHARMACODYNAMICS FOLLOWING ACUTE & CHRONIC ADMINISTRATION

Abstract

Furosemide (F) pharmacodynamics in VLBW infants have not been described following initial and subsequent doses during chronic adminstration. F acts from the luminal side of the loop of Henle and there is a log dose-response relationship between diuretic responses (Na excretion rate, urine output) and F urinary excretion rate. Serial urine collections were performed on 8 VLBW infants begun on F for treatment of BPD. Urine volume and F and sodium concentrations were measured. A linear relationship between diuretic response and F excretion rate was noted in all patients. Natriuretic response (mEq/hr) to initial doses of F decreased significantly with increasing gestational age (p<.02). The F excretion rate required to produce a standard diuretic response was significantly greater (p=.05) during chronic administration than following the initial dose. No consistent pattern of maturation of diuretic response was noted during subsequent chronic administration. We conclude that apparent sensitivity to F decreases with increasing gestational age at the start of therapy and with subsequent chronic doses. These changes may reflect the ability of the renal tubule to compensate for diuretic induced sodium and water loss. Results of previous studies of furosemide pharmacodynamics in VLBW infants following single initial doses can not be extrapolated to chronic administration.