Pharmacology of furosemide in the premature newborn infant

The pharmacokinetic parameters of furosemide were measured in 14 premature newborn infants, one to 20 days of age, and in 12 older infants, aged one to 4 months, following a single intravenous dose of 1 mg/kg of furosemide. Furosemide levels were determined by a high pressure liquid chromatographic method which required 3 microliter of plasma. The volume of distributuion for furosemide was calculated to be 0.24 +/- 0.03 l/kg (mean +/- SE) in all infants studied, regardless of postnatal age. The half-life in the first three weeks of life was found to be 19.9 +/- 3.0 hours. Thus, the half-life of furosemide in the premature infant is considerably longer than in adults or older children, but the volume of distribution is similar. The bioavailability of oral furosemide in infants appeared to be low. The findings of this study indicate that furosemide, 1 mg/kg parenterally, given with a frequency of more than twice daily to the premature infant in the immediate neonatal period, or in parenteral dosages in excess of 2 mg/kg, may lead to plasma levels associated with ototoxicity.