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DELAYED PLASMA CLEARANCE OF FUROSEMIDE WITH MULTIPLE DOSING IN NEONATES

The effect of repeated dosing of IV furosemide (F) on the drug's kinetic profile was evaluated in two groups of neonates; 8 babies with pulmonary edema or fluid overload who received F for the first time (bt wgt 2.3±3 g, gest age 35.0±1.0, postconceptional age 36.6±1 wk) and 7 neonates who received a repeat dose of F, (bt wgt 1.8±0.4, gest age 31.7±2.2, postconceptional age 34.6±2.0 wk), 24-48 hrs after the first dose. Clinical data were not significantly different in between groups. Blood samples for F measured by HPLC were obtained before and at times 1,2,3,6,9,12,24 h after F. Kinetic data were calculated assuming a one compartment open model using areas under the time concentration curve.Data show that repeat doses of F leads to a higher plasma concentration (corrected for pre-drug concentration) contracted volume of distribution and decreased plasma clearance. We postulate that the initial dose saturates tissue binding sites leading to higher drug concentrations and decreased plasma clearance with subsequent doses. Frequent repeat doses of F may lead to plasma drug accumulation in the neonate.