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

Viani, A; Gm, Pacifici

doi:10.1159/000480924

Cited by 4 publications

(3 citation statements)

References 4 publications

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“…Bilirubin displaces furosemide from albumin and the effect is greater in newborn infants than in adult subjects [73,74]. The unbound fraction of furosemide in the plasma of newborn infants was 2.32 ± 0.14, 2.94 ± 0.26 and 3.52 ± 0.38 in the absence, and in presence of 200 µM and 400 µM bilirubin, respectively [73].…”

Section: Resultsmentioning

confidence: 99%

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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%

“…The unbound fraction of furosemide in the plasma of newborn infants was 2.32 ± 0.14, 2.94 ± 0.26 and 3.52 ± 0.38 in the absence, and in presence of 200 µM and 400 µM bilirubin, respectively [73]. The unbound fraction of furosemide was significantly greater in the plasma to which bilirubin was added ( p < 0.001).…”

Section: Resultsmentioning

confidence: 99%

Clinical Pharmacology of Furosemide in Neonates: A Review

Pacifici

2013

Pharmaceuticals

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“…Two pools of plasma were made by combining 2 ml of plasma from individual samples from 10 young and 10 elderly blood donors who were not taking any medication. Aliquots (10 ml) of the pools were transferred to Visking® dialysis tubing (1-8/32"; molecular weight cutoff 5 KDalton; Medicell International Ltd, London, UK) and dialysed against 50 volumes of 0.067 M sodium phosphate buffer (pH 7.4) containing 1 g 1-1 albumin for 18 h. Dialysis was carried out in an ice-bath with continuous stirring as described by Viani & Pacifici (1990). After dialysis, the plasma, referred to as 'dialysed plasma', was used for measuring the binding of diazepam and salicylic acid.…”

Section: Dialysis Ofplasmamentioning

confidence: 99%

The effect of ageing on plasma albumin and plasma protein binding of diazepam, salicylic acid and digitoxin in healthy subjects and patients with renal impairment.

Viani

Rizzo

Carrai

et al. 1992

Brit J Clinical Pharma

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1. Plasma albumin concentration was measured in 118 healthy subjects (aged between 18 and 87 years), in 95 renal patients with creatinine clearances between 15 and 50 ml min‐1 (aged between 14 and 79 years) and in 101 uraemic patients maintained on chronic haemodialysis (aged between 27 and 83 years). 2. There was a significant (P less than 0.001) negative correlation between albumin concentration and age in healthy subjects, but no correlation in patients with low creatinine clearance or in uraemic patients. 3. The ex vivo plasma binding of diazepam (1 microM), salicylic acid (2 mM) and digitoxin (37 nM) was studied in groups of age‐selected young and aged healthy subjects in patients with low creatinine clearance and in patients with uraemia. The unbound fractions of diazepam and salicylic acid were about double in old compared with young healthy subjects whereas they were similar in young and old patients with lowered creatinine clearance. In uraemic patients, ageing did not affect the binding of salicylic acid whereas the unbound fraction of diazepam was slightly but significantly greater in elderly subjects. The unbound fraction of digitoxin was independent of age in both healthy subjects and in those with renal disease. 4. Decreased plasma binding of diazepam and salicylic acid was partially corrected by extensive dialysis of plasma. The lower plasma binding of diazepam and salicylic acid associated with ageing may be ascribed to the effects of endogenous displacers and to hypoalbuminaemia. The influence of these two factors appears to be drug‐dependent.

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Understanding Mechanisms of Food Effect and Developing Reliable PBPK Models Using a Middle-out Approach

Pépin

Huckle

Alluri

et al. 2021

AAPS J

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Over the last 10 years, 40% of approved oral drugs exhibited a significant effect of food on their pharmacokinetics (PK) and currently the only method to characterize the effect of food on drug absorption, which is recognized by the authorities, is to conduct a clinical evaluation. Within the pharmaceutical industry, there is a significant effort to predict the mechanism and clinical relevance of a food effect. Physiologically based pharmacokinetic (PBPK) models combining both drug-specific and physiology-specific data have been used to predict the effect of food on absorption and to reveal the underlying mechanisms. This manuscript provides detailed descriptions of how a middle-out modeling approach, combining bottom-up in vitro-based predictions with limited top-down fitting of key model parameters for clinical data, can be successfully used to predict the magnitude and direction of food effect when it is predicted poorly by a bottom-up approach. For nefazodone, a mechanistic clearance for the gut and liver was added, for furosemide, an absorption window was introduced, and for aprepitant, the biorelevant solubility was refined using multiple solubility measurements. In all cases, these adjustments were supported by literature data and showcased a rational approach to assess the factors limiting absorption and exposure.

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

Cited by 4 publications

References 4 publications

Clinical Pharmacology of Furosemide in Neonates: A Review

Clinical Pharmacology of Furosemide in Neonates: A Review

The effect of ageing on plasma albumin and plasma protein binding of diazepam, salicylic acid and digitoxin in healthy subjects and patients with renal impairment.

Understanding Mechanisms of Food Effect and Developing Reliable PBPK Models Using a Middle-out Approach

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