Serum Protein Binding of Furosemide in
Newborn Infants and Children

Gm, Pacifici; Viani, A; Taddeucci-Brunelli, G

doi:10.1159/000457773

Cited by 15 publications

(10 citation statements)

References 10 publications

(15 reference statements)

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“…In adults, the concentration of albumin was 50.4 ± 6.0 g/L (n = 31; age 34 ± 6 years) and was significantly ( p < 0.001) greater than that in the cord plasma [71]). The unbound fraction of furosemide in the umbilical cord plasma was 2.5 ± 0.1 and in adult plasma was 1.7 ± 0.7 ( p < 0.001; [72]).…”

Section: Resultsmentioning

confidence: 99%

Clinical Pharmacology of Furosemide in Neonates: A Review

Pacifici

2013

Pharmaceuticals

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Furosemide is the diuretic most used in newborn infants. It blocks the Na+-K+-2Cl− symporter in the thick ascending limb of the loop of Henle increasing urinary excretion of Na+ and Cl−. This article aimed to review the published data on the clinical pharmacology of furosemide in neonates to provide a critical, comprehensive, authoritative and, updated survey on the metabolism, pharmacokinetics, pharmacodynamics and side-effects of furosemide in neonates. The bibliographic search was performed using PubMed and EMBASE databases as search engines; January 2013 was the cutoff point. Furosemide half-life (t1/2) is 6 to 20-fold longer, clearance (Cl) is 1.2 to 14-fold smaller and volume of distribution (Vd) is 1.3 to 6-fold larger than the adult values. t1/2 shortens and Cl increases as the neonatal maturation proceeds. Continuous intravenous infusion of furosemide yields more controlled diuresis than the intermittent intravenous infusion. Furosemide may be administered by inhalation to infants with chronic lung disease to improve pulmonary mechanics. Furosemide stimulates prostaglandin E2 synthesis, a potent dilator of the patent ductus arteriosus, and the administration of furosemide to any preterm infants should be carefully weighed against the risk of precipitation of a symptomatic patent ductus arteriosus. Infants with low birthweight treated with chronic furosemide are at risk for the development of intra-renal calcifications.

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Section: Resultsmentioning

confidence: 99%

Clinical Pharmacology of Furosemide in Neonates: A Review

Pacifici

2013

Pharmaceuticals

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“…Recent articles from dif ferent groups [1,10,12] and also from our group [11] have shown that the unbound fraction of furosemide is significantly higher in cord than adult serum. A number of re views have attributed importance to the un bound concentration of drugs rather than the TSP = Total serum protein; NEFA = nonesterified fatty acids; TB = total serum bilirubin; UB = unconju gated bilirubin; ND = not determined.…”

mentioning

confidence: 66%

“…The binding assay was carried out as previously described [11]. Briefly, furosemide was dissolved in methanol and added in 0.5 pi to 1 ml of buffer (0.067 M sodium orthophosphate, pH 7.4) to give a final furosemide concentration of 2 pg/ml.…”

Section: Assaymentioning

confidence: 99%

Bilirubin Displaces Furosemide from Serum Protein: The Effect Is Greater in Newborn Infants than Adult Subjects

Viani

Gm²

1990

Dev Pharmacol Ther

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The protein binding of furosemide was studied in the serum from 7 umbilical cords and 7 healthy adult subjects in presence or absence of bilirubin. In cord serum, the unbound fraction of furosemide (mean ± SD) was 2.32 ± 0.14 (control), 2.94 ± 0.26 (200 μM bilirubin) (p < 0.001) and 3.52 ± 0.38 (400 μM bilirubin) (p < 0.001). Percent increase (mean ± SD) of the unbound furosemide was 22 ±11 and 51 ± 12 after 200 and 400 μM bilirubin, respectively. In adult serum, the unbound fraction of furosemide was 1.69 ± 0.21 (control), 1.93 ± 0.24 (200 μM bilirubin) and 2.15 ± 0.38 (400 μM bilirubin). Percent increase of the unbound fraction was 14 ± 8 and 28 ± 16 after 200 and 400 μM bilirubin, respectively. Binding of furosemide was also studied in 5 cord and adult serum specimens previously dialysed for 18 h at 4 °C. Unbound furosemide in dialyzed serum was 1.39 ± 0.05 (cord) and 1.25 ± 0.04 (adult). Cord serum contains dialyzable compounds that enhance the unbound fraction of furosemide. Displacement effect of bilirubin was unchanged by dialysis and it was significantly higher in cord than adult serum. The different displacing effect of bilirubin might suggest the presence of qualitatively different albumin in cord serum.

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“…Aliquots (0.7 ml) of albu min were dialyzed against the same volume of 0.13 M sodium orthophosphate buffer (pH 7.4) containing 2 pg/ml (6 pM) [14C]furosemide (135,OOOdpm; added in 0.5 pi methanol) at 37 °C for 4 h in a Dia nomi apparatus (Diachema, Zurich, Switzerland). Equilibrium was reached after 2 h and the bound frac tion of furosemide was constant for at least up to 4 h. Although the unbound fraction of furosemide in creases with the molarity of the sodium orthophos phate buffer [12], a higher buffer molarity than pre viously [6] was used because of the interaction study with bilirubin which was added in 10 pi of 0.05 M NaOH per milliliter buffer. Thus, 0.13 M sodium orthophosphate buffer was used throughout the study.…”

Section: Methodsmentioning

confidence: 99%

Binding of Furosemide to Albumin Isolated from Human Fetal and Adult Serum

Viani

Cappiello²,

Silvestri³

et al. 1991

Dev Pharmacol Ther

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Albumin was isolated from pooled fetal serum from 58 placentas obtained at normal delivery at term and from pooled adult plasma from 8 individuals. Albumin isolation was carried out by means of PEG precipitation followed by ion-exchange chromatography on DEAE-Sephadex A 50 and then on SP-Sephadex C 50. The electrophoresis on SDS-polyacrylamide gels showed only one spot that comigrated with commercial human albumin. Binding to albumin was measured by equilibrium dialysis of an aliquot of albumin solution (0.7 ml) against the same volume of 0.13 M sodium orthophosphate buffer (pH 7.4). At a total concentration of 2 μg/ml (therapeutic range), the unbound fraction of furosemide was 2.71 % (fetal albumin) and 2.51 % (adult albumin). Two classes of binding sites for furosemide were observed in fetal and adult albumin. The number of binding sites (moles of furosemide per mole of albumin) was 1.22 (fetal albumin) and 1.58 (adult albumin) for the high-affinity site and 2.97 (fetal albumin) and 3.25 (adult albumin) for the low-affinity site. The association constants (M^-1 ) were 3.1 X 10^4 (fetal albumin) and 2.6 X 10^4 (adult albumin) for the high-affinity set of sites and 0.83 X 10^4 (fetal albumin) and 1.0 X 10^4 (adult albumin) low-affinity site. The displacement of furosemide from albumin was studied with therapeutic concentrations of several drugs. Valproic acid, salicylic acid, azapropazone and tolbutamide had the highest displacing effects which were significantly higher with fetal than with adult albumin.

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Serum Protein Binding of Furosemide in Newborn Infants and Children

Cited by 15 publications

References 10 publications

Clinical Pharmacology of Furosemide in Neonates: A Review

Clinical Pharmacology of Furosemide in Neonates: A Review

Bilirubin Displaces Furosemide from Serum Protein: The Effect Is Greater in Newborn Infants than Adult Subjects

Binding of Furosemide to Albumin Isolated from Human Fetal and Adult Serum

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