Plasma and urinary kinetics of furosemide in newborn infants

doi:10.1016/S0022-3476(83)80433-8

The Journal of Pediatrics

Volume 103, Issue 3, September 1983, Pages 481-485

https://doi.org/10.1016/S0022-3476(83)80433-8 Get rights and content

Plasma and urinary furosemide kinetics were assayed by high-power liquid chromatography in six newborn infants receiving furosemide (1 mg/kg body weight IV) for the treatment of fluid overload. Mean±SD for plasma half-life, apparent volume of distribution, and plasma clearance were, respectively, 9.5±4.4 hours, 173±28 ml/kg, and 15.3±8.4 ml/hr/kg. There was close correspondence between plasma and urinary half-lives and between plasma clearance and renal clearance. In the first 24 hours, mean estimated urinary recovery of unchanged furosemide was 90% of the injected dose (range 61% to 106%). The results suggest that in the newborn infant furosemide is virtually all excreted unchanged in the urine and that the absence of significant nonrenal elimination, together with the immaturity of neonatal renal function, accounts for its prolonged half-life in newborn infants.

References (22)

RossBS et al.
The pharmacologic effects of furosemide therapy on the low-birth-weight infant
J Pediatr
(1978)
ChennavasinP et al.
Pharmacodynamic analysis of the furosemide-probenecid interaction in man
Kidney Int
(1979)
ArandaJV et al.
Pharmacokinetic disposition and protein binding of furosemide in newborn infants
J Pediatr
(1978)
PetersonRG et al.
Pharmacology of furosemide in the premature newborn infant
J Pediatr
(1980)
ArandaJV et al.
Metabolism and renal elimination of furosemide in the newborn infant
J Pediatr
(1982)
RaneA
Urinary excretion of diphenylhydantoin metabolites in newborn infants
J Pediatr
(1974)
WooW-CR et al.
Effects of furosemide in the newborn
Clin Pharmacol Ther
(1978)
RuppW
Pharmacokinetics and pharmacodynamics of lasix
Scot Med J
(1974)
BeermannB et al.
Elimination of furosemide in healthy subjects and in those with renal failure
Clin Pharmacol Ther
(1977)
RaneV et al.
Plasma binding and disposition of furosemide in the nephrotic syndrome and in uremia
Clin Pharmacol Ther
(1978)

VertP et al.

Pharmacokinetics of furosemide in neonates

Eur J Clin Pharmacol

(1982)

Cited by (39)

Effect of probenecid on blood levels and renal elimination of furosemide and endogenous compounds in rats: Discovery of putative organic anion transporter biomarkers
2023, Biochemical Pharmacology
Transporter-mediated drug-drug interactions (DDIs) are assessed using probe drugs and in vitro and in vivo models during drug development. The utility of endogenous metabolites as transporter biomarkers is emerging for prediction of DDIs during early phases of clinical trials. Endogenous metabolites such as pyridoxic acid and kynurenic acid have shown potential to predict DDIs mediated by organic anion transporters (OAT1 and OAT3). However, these metabolites have not been assessed in rats as potential transporter biomarkers. We carried out a rat pharmacokinetic DDI study using probenecid and furosemide as OAT inhibitor and substrate, respectively. Probenecid administration led to a 3.8-fold increase in the blood concentrations and a 3-fold decrease in renal clearance of furosemide. High inter-individual and intra-day variability in pyridoxic acid and kynurenic acid, and no or moderate effect of probenecid administration on these metabolites suggest their limited utility for prediction of Oat-mediated DDI in rats. Therefore, rat blood and urine samples were further analysed using untargeted metabolomics. Twenty-one m/z features (out of >8000 detected features) were identified as putative biomarkers of rat Oat1 and Oat3 using a robust biomarker qualification approach. These m/z features belong to metabolic pathways such as fatty acid analogues, peptides, prostaglandin analogues, bile acid derivatives, flavonoids, phytoconstituents, and steroids, and can be used as a panel to decrease variability caused by processes other than Oats. When validated, these putative biomarkers will be useful in predicting DDIs caused by Oats in rats.
Diuretics and Invasive Fluid Management Strategies
2018, Heart Failure in the Child and Young Adult: From Bench to Bedside
Congestion is one of the most common clinical features of heart failure. Fluid overload may occur in patients with acute or chronic heart failure and can lead to symptoms independent of cardiac output. Among children, signs and symptoms of congestion frequently include hepatomegaly, abdominal pain, gallop heart rhythm, poor appetite, tachypnea, and wheezing. Peripheral edema, hyponatremia, and jugular venous distention occur in more advanced stages of heart failure. Symptomatic relief may be obtained with diuresis as cardiac filling pressures are lowered and extravascular fluid is mobilized from the lungs and peripheral tissues. Cardiac performance may also improve with diuresis as left ventricular end-diastolic pressure is reduced and mitral regurgitation is decreased (Ramierez and Abelmann, 1968).
Lack of Furosemide Responsiveness Predicts Acute Kidney Injury in Infants After Cardiac Surgery
2017, Annals of Thoracic Surgery
Citation Excerpt :
2) We were unable to interpret the urine output beyond 6 hours after the initial dose of furosemide as additional doses of diuretics are typically administered and urine output precision would decrease with urinary catheter removal. Studies evaluating the kinetics of furosemide suggest slower clearance of furosemide in infants as compared with that in adults [26, 27]. Many of our patients received additional doses of diuretics beyond 6 hours from the initial dose.
This was a retrospective study to determine whether lack of furosemide responsiveness (LFR) predicts acute kidney injury (AKI) after cardiopulmonary bypass surgery in infants.
Infants (less than 1 year of age) undergoing cardiopulmonary bypass surgery, receiving routine postoperative furosemide (0.8 to 1.2 mg/kg per dose between 8 and 24 hours after surgery) were included. Urine output was measured 2 and 6 hours after furosemide dose. Lack of furosemide responsiveness was defined a priori as urine output less than 1 mL · kg⁻¹ · h⁻¹ after furosemide. Serum creatinine was corrected for fluid balance. Acute kidney injury was determined using changes in uncorrected and corrected serum creatinine. The predictive utility of LFR was assessed using receiver-operating characteristics curve analysis.
We analyzed 568 infants who underwent cardiopulmonary bypass. Eighty-one (14.3%) had AKI using uncorrected serum creatinine; AKI occurred in 41 (7.2%) after correcting for fluid overload. Patients with AKI had a lower response to furosemide (median urine output 2 hours: 1.2 versus 3.4 mL · kg⁻¹ · h⁻¹, p = 0.01; median urine output 6 hours: 1.3 versus 2.9 mL · kg⁻¹ · h⁻¹, p = 0.01). After creatinine correction, LFR predicts AKI development (area under receiver-operating characteristics curve of 0.74 at 2 hours and 0.77 at 6 hours). After adjusting for surgical complexity using The Society of Thoracic Surgeons/European Association for Cardiothoracic Surgery mortality categories, the area under the receiver-operating characteristics curve was 0.74 at 2 hours and 0.81 at 6 hours. Patients with urine output greater than 1 mL · kg⁻¹ · h⁻¹ were unlikely to have AKI (negative predictive value, 97%).
After correcting serum creatinine for fluid balance and adjusting for surgical complexity, LFR performs fairly at 2 hours, whereas at 6 hours, LFR is a good AKI predictor. Prospective studies are needed to validate whether diuretic responsiveness predicts AKI.
Diuretics and Invasive Fluid Management Strategies
2017, Heart Failure in the Child and Young Adult: From Bench to Bedside
Congestion is one of the most common clinical features of heart failure. Fluid overload may occur in patients with acute or chronic heart failure and can lead to symptoms independent of cardiac output. Among children, signs and symptoms of congestion frequently include hepatomegaly, abdominal pain, gallop heart rhythm, poor appetite, tachypnea, and wheezing. Peripheral edema, hyponatremia, and jugular venous distention occur in more advanced stages of heart failure. Symptomatic relief may be obtained with diuresis as cardiac filling pressures are lowered and extravascular fluid is mobilized from the lungs and peripheral tissues. Cardiac performance may also improve with diuresis as left ventricular end-diastolic pressure is reduced and mitral regurgitation is decreased (Ramierez and Abelmann, 1968).
Pharmacotherapy Review of Chronic Pediatric Hypertension
2011, Clinical Therapeutics
Citation Excerpt :
With the exception of neonates, studies evaluating the treatment of pediatric hypertension with loop diuretics were not found. Studies in neonates focus on the pharmacokinetics of furosemide.114–117 Thiazide diuretics, such as chlorothiazide and hydrochlorothiazide, have also been used in the pediatric population, although no studies were found to support their use in treating pediatric hypertension.
The number of antihypertensive agents on the market has increased dramatically over the past 20 years. Many of these agents are used to treat children and adolescents with hypertension despite there being relatively limited data available supporting such use. Recent legislation has helped to increase the number of studies conducted in children, but many clinical questions remain unanswered.
The goals of this article were to review the currently available antihypertensive agents used in the treatment of pediatric hypertension and to assist clinicians in selecting the most appropriate treatment.
Searches of MEDLINE and International Pharmaceutical Abstracts through July 2011 were conducted. Search terms used included child, pediatric, hypertension, and the following drugs: captopril, enalapril, lisinopril, fosinopril, losartan, valsartan, irbesartan, candesartan, olmesartan, amlodipine, nifedipine, isradipine, felodipine, propranolol, metoprolol, labetalol, minoxidil, furosemide, spironolactone, chlorothiazide, hydrochlorothiazide, hydralazine, and prazosin. Clinical trial data were reviewed and evaluated and were limited to English-language articles.
A total of 45 observational and randomized controlled trials were identified and summarized in this review. The angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel antagonists (CCAs) had the strongest data to support their use in pediatric patients. ACE inhibitors and ARBs are preferred agents for children with renal disease and have a favorable safety profile. Many trials, including 2 comparative trials, supported the use of CCAs, particularly amlodipine, in children.
Trials in all 3 classes suggested their efficacy as well as a tolerable adverse-effect profile. More trials in children are needed, particularly with newer antihypertensive agents. Comparative trials of different agents are the most lacking.
Diuretic therapy of heart failure in infants and children
2000, Progress in Pediatric Cardiology
Diuretics are the mainstay of traditional therapy for congestive heart failure. The syndrome of heart failure is now understood to involve complex interactions of neurohumoral substances released in response to poor cardiac function. Developmental changes during infancy and childhood will affect both the activation of systemic neurohumoral responses and the pharmacokinetic and pharmacodynamic actions of diuretics. Few human studies directly evaluate the efficacy of diuretic therapy in heart failure in adults. The pharmacodevelopmental aspects of diuretic therapy in infants and children are also incompletely studied. This review will describe the kidney's role in the pathogenesis of sodium and water retention in heart failure and the developmental changes in the kidney related to fluid retention. Known principles of diuretic therapy in congestive heart failure will be described. All these factors can then be used by the reader to evaluate the role of diuretic therapy in the complex syndrome of heart failure in infants and children.

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Plasma and urinary kinetics of furosemide in newborn infants

J Pediatr

Kidney Int

J Pediatr

J Pediatr

J Pediatr

J Pediatr

Effects of furosemide in the newborn

Clin Pharmacol Ther

Pharmacokinetics and pharmacodynamics of lasix

Scot Med J

Elimination of furosemide in healthy subjects and in those with renal failure

Clin Pharmacol Ther

Plasma binding and disposition of furosemide in the nephrotic syndrome and in uremia

Clin Pharmacol Ther

Pharmacokinetics of furosemide in neonates

Eur J Clin Pharmacol