1045 Protein Binding and Pharmacokinetic Disposition of Furosemide (F) in Newborn Infants

Abstract

The pharmacokinetic disposition of F was studied in 8 premature and full-term neonates with fluid overload using a one compartment model. Mean (+S.E.) birth weight was 2391.3 + 289.9 g; gestational age was 35.0 + 1.8 wks and postnatal age was 11.5 f 5.9 days. BUN was 10.4 f 1.5 mg/dl and serum creatinine was 0.9 mgldl. Following a single IV dose of F, (1-1.5 mglkg) blood samples (0.2 mllsample) were obtained from a heelstick or an arterial catheter at times 0, 0.5, 1,2,4,6,9,12 and 24 hrs and analyzed for F, measured by gas liquid chromatograph . The m a n (+S.E volume of distribution was 829.2 t118.9 *.kg-I; Tb was 7.7 + 1.0 h; elimination rate constant (Kel) was 0.102 + 0.013h-1 and plasma clearance was 81.61 f 14.98 ml.kg-1.h-1. Compared to the disposition of F in normal adults, aVd is almost 4-fold greater in the neonate with an 8-fold prolongation in plasma Tt, an 8-fold decrease in Kel and a 2-fold decrease in plasma clearance. Neither gestational and postnatal age nor birth weight correlated with the pharmacokinetic variables. F had no effect on the reserve bilirubin binding capacity (RBBC) measured by sephadexgel filtration in 6 neonates (age 2.1 + 0.3 d; weight 2329.9 + 339.1 g) . Hean RBBC 5 min before and 30-60 min agter F were 6.2+ 0.2 and 6.8 + 0.5 mgldl respectively. Slow F elimination may par tly explain the prolonged diuretic and saluretic effect of F in the neonate. This must be taken into account whenever repetitive The developing kidney has been reported to have a limited capacity compared to the adult to excrete an acutely administered sodium load. Studies to date have presumed that the sodium administered is filtered and reabsorbed by the nephron. Preliminary studies of human infants in our laboratory indicated that fractional sodium excretion(FE ) varied with Posm and with fractional urine flow (V/GFR).N?he present study was designed to compare renal sodium excretion in puppies during the first month of life for 2 hours following IV saline loading(lOml/kg) given as (A) 0.9% saline(NS), (B) 10% albuminINS or (C) 10% glucose/ NS. Results are presented from studies completed to date as mean per cent changes from control values. and T. York, Depts.of Anatomy & Human Development, Mich. State University (Spons. bv M. Bailie), East Lansinq, Michigan.The increased incidence of severe systemic infections in INSC secondary to bacteria with polysaccharide capsules suqgests a d e fect in serum complement activity relatins to chemotactic activity. Chemotactic function was assessed in INSC durino 1)"severe" relapse, 2) "mild" relapse, & 3 ) "remission" with respect to A) chemotactic activity generated by INSC sera (fzymosan activation) B)chemotactic responses of INSC PMNs to control sera, & Clinhibitory effects of INSC sera and/or plasma on control PMNs (modified Bovden method). Serum chemotactic activity in 14 "severe8'rrlaosinq INSC patients was diminished compared to controls (D < 0.01) and 21 "mild" and "remission" patients (p<0.001). Chemotactic activity of zymosan activated sera was diminished comp...