Cumulative Increase in Serum Furosemide Concentration Following Repeated Doses in the Newborn

ABSTRACT

In order to test whether repeat doses of the diuretic furosemide result in plasma accumulation of this drug, eight newborns (mean birthweight, 1252 gm; mean gesta-tional age, 27.5 weeks; mean postnatal age, 44.7 days; and normal renal function) were each given a 1-mg/kg iv bolus every 12 hr for four doses and maintained normally hydrated throughout the study period. Serum furosemide peak concentrations (1 hr after administration) were measured in eight newborns, and trough levels in four newborns, by HPLC. The mean 1-hr serum furosemide level increased with repeated doses of the drug, from 3.18 ± 0.52 to 7.95 ± 2.36 mg/liter (mean ± SE) (p < .05). In contrast, the mean serum trough concentration of furosemide remained at a plateau following the first dose (1.8 ± 0.82 to 1.98 ± 1.81 mg/liter), suggesting attainment of a steady state. This accumulation of furosemide following repeated doses of this diuretic, therefore, reflects the decreased plasma clearance of the drug, possibly due to contraction of its volume of distribution.