Pharmacokinetics of bumetanide in critically ill infants*

Sullivan, Janice E.; Witte, Madolin K.; Yamashita, Toyoko S.; Myers, Carolyn M.; Blumer, Jeffrey L.

doi:10.1016/s0009-9236(96)90197-6

Cited by 47 publications

(51 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Decreased plasma clearance and increased volume of distribution are probably responsible for the prolongation of half-life. Full-term infants have half-lives that are double the normal adult values [91]. The half-life of bumetanide decreases with increasing postnatal age due to increases in plasma clearance, but remains greater than adult values because distribution volumes in infants are higher than in adults [99].…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…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%

“…Additional metabolites are eliminated by conjugation and biliary excretion [17]. Plasma clearance of bumetanide is dramatically lower in preterm newborns than in term newborns and adults (Table 2) [88,90,91]. Although plasma clearance in term newborns is still less than adult values, it has been shown to increase proportionally with postnatal ages >1 month [99].…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…Therefore, the true metabolic fate of bumetanide in newborns is currently unknown. Renal clearance of bumetanide increases threefold from birth to 6 months of age in full-term infants [91]. As with furosemide, maturation of tubular secretory function is most likely responsible for the increased urinary excretion [91].…”

Section: Pharmacokineticsmentioning

confidence: 99%

See 3 more Smart Citations

The clinical pharmacology of loop diuretics in the pediatric patient

Eades

Christensen

1998

Pediatric Nephrology

View full text Add to dashboard Cite

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.

show abstract

Section: Pharmacokineticsmentioning

confidence: 99%

Section: Pharmacokineticsmentioning

confidence: 99%

Section: Pharmacokineticsmentioning

confidence: 99%

Section: Pharmacokineticsmentioning

confidence: 99%

See 2 more Smart Citations

The clinical pharmacology of loop diuretics in the pediatric patient

Eades

Christensen

1998

Pediatric Nephrology

View full text Add to dashboard Cite

show abstract

“…Bumetanide has been extensively used in both healthy and critically ill human full-term and preterm infants to treat fluid volume overload due to cardiac and/or pulmonary disease, so extrapolation from these studies might help guide the design of any potential pilot studies or clinical trials. 43,72 However, it will be important to investigate whether the pharmacokinetics of bumetanide are altered by any of the underlying diseases that are responsible for triggering seizures in neonates, because many full-term newborns with refractory seizures have hypoxic-ischemic encephalopathy from perinatal asphyxia, which is often accompanied by multiorgan dysfunction (including hepatic and renal failure); such organ dysfunction can dramatically affect drug metabolism. 12,47,73 Perhaps the best new treatment strategy for neonatal seizures and one that could be easily tested, is a combination regimen that would include bumetanide with a barbiturate like phenobarbital.…”

Section: Bridging the Gap From Animal Models Of Neonatal Seizures To mentioning

confidence: 99%

The bumetanide-sensitive Na-K-2Cl cotransporter NKCC1 as a potential target of a novel mechanism-based treatment strategy for neonatal seizures

Kahle¹,

Staley

2008

FOC

106

View full text Add to dashboard Cite

Seizures that occur during the neonatal period do so with a greater frequency than at any other age, have profound consequences for cognitive and motor development, and are difficult to treat with the existing series of antiepileptic drugs. During development, γ-aminobutyric acid (GABA)ergic neurotransmission undergoes a switch from excitatory to inhibitory due to a reversal of neuronal chloride (Cl–) gradients. The intracellular level of chloride ([Cl–]i) in immature neonatal neurons, compared with mature adult neurons, is about 20–40 mM higher due to robust activity of the chloride-importing Na-K-2Cl cotransporter NKCC1, such that the binding of GABA to ligand-gated GABAA receptor-associated Cl– channels triggers Cl– efflux and depolarizing excitation. In adults, NKCC1 expression decreases and the expression of the genetically related chloride-extruding K-Cl cotransporter KCC2 increases, lowering [Cl–]i to a level such that activation of GABAA receptors triggers Cl– influx and inhibitory hyperpolarization. The excitatory action of GABA in neonates, while playing an important role in neuronal development and synaptogenesis, accounts for the decreased seizure threshold, increased seizure propensity, and poor efficacy of GABAergic anticonvulsants in this age group. Bumetanide, a furosemide-related diuretic already used to treat volume overload in neonates, is a specific inhibitor of NKCC1 at low doses, can switch the GABA equilibrium potential of immature neurons from depolarizing to hyperpolarizing, and has recently been shown to inhibit epileptic activity in vitro and in vivo in animal models of neonatal seizures. The fundamental role of NKCC1 in establishing excitatory GABAergic neurotransmission in the neonate makes it a tempting target of a novel mechanism-based anticonvulsant strategy that could utilize the well-known pharmacology of bumetanide to help treat neonatal seizures.