Kaoru Okazaki1,2, Noriyasu Fukuoka3, Toru Kuboi1, Jun Unemoto2, Masatoshi Kondo2, Takashi Kusaka4, Susumu Itoh4. 1. Department of Neonatology, Shikoku Medical Center for Children and Adults, Kagawa, Japan. 2. Department of Neonatology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan. 3. Laboratory of Hospital Pharmacy, School of Pharmacy, Nihon University, Chiba, Japan. 4. Department of Pediatrics, Kagawa University, Kagawa, Japan.
Abstract
BACKGROUND: Furosemide is an off-label drug, frequently used as a diuretic in neonates with oliguria and/or edema. Its clearance in preterm neonates is lower than in term neonates or children. We aimed, herein, to clarify furosemide clearance (CL) in very preterm (VP) neonates (<28 weeks' gestation) within the first 2 weeks of life and identify the factors predictive of the pharmacokinetics (PK) parameters, such as CL. METHODS: Furosemide was administered at 0.5 or 1 mg/kg in a 0.5-h infusion via a syringe pump; blood samples were drawn from an artery or vein after the intravenous injection. The serum furosemide concentration was measured using high-performance liquid chromatography. The PK parameters were then analyzed using Bayesian estimation. RESULTS: Thirteen blood samples were obtained from 10 VP neonates after intravenous injection. The mean postconceptional age and mean postnatal days at exposure to furosemide were 26.9 weeks and 7.1 days, respectively. The estimated mean CL was 16.5 mL/kg/h. The mean distribution volume (Vd) and elimination half-life (t1/2) were 0.37 L/kg and 15.3 h, respectively. Furosemide CL was negatively associated with serum creatinine (SCr) [CL = 84.2 - 67.1 × SCr (mg/dL)]. CONCLUSIONS: Very preterm neonates within the first 2 weeks of life had a higher CL than subjects in other preterm neonatal studies. The SCr level was the sole parameter influencing furosemide CL and might serve as a good index for furosemide dosing in VP neonates.
BACKGROUND: Furosemide is an off-label drug, frequently used as a diuretic in neonates with oliguria and/or edema. Its clearance in preterm neonates is lower than in term neonates or children. We aimed, herein, to clarify furosemide clearance (CL) in very preterm (VP) neonates (<28 weeks' gestation) within the first 2 weeks of life and identify the factors predictive of the pharmacokinetics (PK) parameters, such as CL. METHODS: Furosemide was administered at 0.5 or 1 mg/kg in a 0.5-h infusion via a syringe pump; blood samples were drawn from an artery or vein after the intravenous injection. The serum furosemide concentration was measured using high-performance liquid chromatography. The PK parameters were then analyzed using Bayesian estimation. RESULTS: Thirteen blood samples were obtained from 10 VP neonates after intravenous injection. The mean postconceptional age and mean postnatal days at exposure to furosemide were 26.9 weeks and 7.1 days, respectively. The estimated mean CL was 16.5 mL/kg/h. The mean distribution volume (Vd) and elimination half-life (t1/2) were 0.37 L/kg and 15.3 h, respectively. Furosemide CL was negatively associated with serum creatinine (SCr) [CL = 84.2 - 67.1 × SCr (mg/dL)]. CONCLUSIONS: Very preterm neonates within the first 2 weeks of life had a higher CL than subjects in other preterm neonatal studies. The SCr level was the sole parameter influencing furosemide CL and might serve as a good index for furosemide dosing in VP neonates.
Authors: Nicolas A Bamat; Elizabeth J Thompson; Rachel G Greenberg; Scott A Lorch; Athena F Zuppa; Eric C Eichenwald; Veeral N Tolia; Reese H Clark; P Brian Smith; Christoph P Hornik; Jason E Lang; Matthew M Laughon Journal: J Perinatol Date: 2022-01-24 Impact factor: 3.225