Metabolism and renal elimination of furosemide in the newborn infant

Aranda, Jacob V.; Lambert, Chantal; Perez, J.; Türmen, Tomris; Sitar, Daniel S.

doi:10.1016/s0022-3476(82)80319-3

Cited by 35 publications

(26 citation statements)

References 15 publications

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“…(Pa tient 7, who received 16.4 mg/kg F, patient 8, who was 23 months old, and patients 10 and 14, who received the drug intramuscularly, were excluded from the calculations.) Such comparison is possible since the dose of 40 mg of F in an adult is roughly proportional to 1 mg/kg in an infant, based on the body surface area; similar comparison was also presented by Aranda et al [3] concerning the newborn infant.…”

Section: Kinetics Of F Elimination With Urinesupporting

confidence: 55%

“…This method, however, is not specific for detection of the parent drug alone, since a small portion of the major metabolites of F, F glucuronide, and 4-chloro-5-suIfamoylanthranilic acid, will also be extracted with the drug [1,22,26]. Although Smith et al [27] found no evidence of this acid metabolite in any of the urine samples from the healthy adult volunteers, further study by Aranda et al [3] involving the use of gas-liquid chromatography did show, however, that newborn infants can metabolize F into this metabolite. Nevertheless, we proved suf ficient specificity of our analytic procedure with use of a recently developed high pressure liquid chromatographic method.…”

Section: Study Proceduresmentioning

confidence: 99%

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Kinetics of Urinary Furosemide Elimination in Infants

Prandota¹,

Houin²

1984

Dev Pharmacol Ther

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Using a one-compartment model, the urinary elimination kinetics of a single intravenous 1 mg/kg dose of furosemide (F) was studied in 13 infants, 9 days to 12 months old (mean 3.7 ± (SD) 3.48 months old), and 1, 23-month-old child, with bilateral multifocal pneumonia, recovering from respiratory and cardiac insufficiency accompanying pneumonia and/or other diseases. F elimination half-life was determined with the use of a noninvasive method based on the drug’s urinary excretion data. The drug urinary elimination t(½) in the infants ranged from 0.654 to 3.29 h. Cumulative excretion of F in the infants' urine was similar to the values in healthy adults. Since the furosemide urinary half-lives found in infants were similar to the data reported in older children and healthy adults it is suggested that immaturity of renal function during the 1st year of life, i.e. in older infants, has no evident effect on the elimination kinetics of a 1 mg/kg intravenous dose of F. Mean F urinary elimination t(½) in infants with pneumonia and cardiac insufficiency was significantly longer compared with the F(t½) found in children with the pneumonia alone (2.15 vs. 1.01 h, respectively), suggesting slower elimination of the drug in these patients.

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Section: Kinetics Of F Elimination With Urinesupporting

confidence: 55%

Section: Study Proceduresmentioning

confidence: 99%

Kinetics of Urinary Furosemide Elimination in Infants

Prandota¹,

Houin²

1984

Dev Pharmacol Ther

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“…Immature renal and hepatic function can change the disposition of loop diuretics in infants compared with older children and adults [85]; therefore, preterm and term infants have been the focus of most pharmacokinetic studies in the pediatric population [12,13,[85][86][87][88][89][90][91][92]. Pediatric pharmacokinetic parameters for furosemide and bumetanide are summarized in Tables 1 and 2, respectively.…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…In adults and older infants, nonrenal elimination of furosemide accounts for about 50% of plasma clearance [16,82,93,94]. Nonrenal clearance is primarily the result of extrahepatic glucuronidation [95,96], which probably occurs in the kidney tubule cells [97], and formation of the acid metabolite CSA (4-chloro-5-sulfamoyl-anthranilic acid) [83,87]. Results of studies evaluating nonrenal elimination in newborns have been conflicting and have not clearly established a correlation between age and the ability to metabolize the drug [85,87].…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…Nonrenal clearance is primarily the result of extrahepatic glucuronidation [95,96], which probably occurs in the kidney tubule cells [97], and formation of the acid metabolite CSA (4-chloro-5-sulfamoyl-anthranilic acid) [83,87]. Results of studies evaluating nonrenal elimination in newborns have been conflicting and have not clearly established a correlation between age and the ability to metabolize the drug [85,87]. Tuck et al [85] reported GA, gestational age; PNA, postnatal age; C p , plasma clearance; C r , renal clearance; t 1/2 , half-life; Vd, volume of distribution; % PB, percent age plasma protein binding; ND, not determined a Values represent mean±SD unless indicated& / t b l .…”

Section: Pharmacokineticsmentioning

confidence: 99%

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The clinical pharmacology of loop diuretics in the pediatric patient

Eades

Christensen

1998

Pediatric Nephrology

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The loop diuretics furosemide and bumetanide are frequently employed in the pediatric population for the management of fluid overload in both acute and chronic disease states. They act mainly by inhibiting sodium reabsorption in the nephron at the thick ascending limb of Henle's loop. Important pharmacokinetic differences between adults and infants include a reduced clearance and prolonged half-life, that may cause accumulation of these agents to potentially toxic levels if dosing intervals are not adjusted. Unfortunately, little is known about the time required for maturation of loop diuretic elimination in older infants, children, and adolescents. Similar to adults, limited pharmacodynamic evidence in neonates suggests that a maximally efficient diuretic dose exists. Increasing the diuretic dose beyond this maximum does not offer further benefit, but may increase the risk of toxicity. Common problems encountered in the pediatric patient as well as in adults are loop diuretic tolerance and resistance. Loop diuretic dosing strategies aimed at overcoming these phenomena include administration by continuous infusion, coadministration with albumin, and coadministration with metolazone or thiazides. This article reviews the pharmacology, pharmacokinetics, and pharmacodynamics of furosemide and bumetanide in pediatric patients. A better understanding of the clinical pharmacology of the loop diuretics should aid clinicians in the development of dosing regimens aimed at producing adequate diuresis without promoting excessive diuretic tolerance.

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Development, validation, and implementation of an UHPLC–MS/MS method for the quantitation of furosemide in infant urine samples

Vedar

Bamat

Zuppa

et al. 2021

Biomedical Chromatography

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Furosemide is a diuretic drug used to increase urine flow in order to reduce the amount of salt and water in the body. It is commonly utilized to treat preterm infants with chronic lung disease of prematurity. There is a need for a simple and reliable quantitation of furosemide in human urine. We have developed and validated an ultra-high performance liquid chromatography-tandem mass spectrometry method for furosemide quantitation in human urine with an assay range of 0.100-50.0 μg/ml. Sample preparation involved solid-phase extraction with 10 μl of urine.Intra-day accuracies and precisions for the quality control samples were 94.5-106 and 1.86-10.2%, respectively, while inter-day accuracies and precision were 99.2-102 and 3.38-7.41%, respectively. Recovery for furosemide had an average of 23.8%, with an average matrix effect of 101%. Furosemide was stable in human urine under the assay conditions. Stability for furosemide was shown at 1 week (room temperature, 4, À20 and À78 C), 6 months (À78 C), and through three freeze-thaw cycles. This robust assay demonstrates accurate and precise quantitation of furosemide in a small volume (10 μl) of human urine. It is currently being implemented in an ongoing pediatric clinical study.

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Metabolism and renal elimination of furosemide in the newborn infant

Cited by 35 publications

References 15 publications

Kinetics of Urinary Furosemide Elimination in Infants

Kinetics of Urinary Furosemide Elimination in Infants

The clinical pharmacology of loop diuretics in the pediatric patient

Development, validation, and implementation of an UHPLC–MS/MS method for the quantitation of furosemide in infant urine samples

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