The pharmacokinetics and pharmacodynamics of bumetanide in normal subjects

Marcantonio, Laurence A.; Auld, William; Skellern, G.G.; Howes, Christine A.; Murdoch, W. R.; Purohit, Rameshwar

doi:10.1007/bf01065171

Cited by 28 publications

(21 citation statements)

References 12 publications

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“…This paper describes the pharmacokinetics and pharmacodynamics of bumetanide when given orally and intravenously to a group of patients with chronic renal failure and to another group with cirrhosis of the liver. The results are compared with those previously obtained by us (Marcantonio et al, 1982) Hepatic group Eight patients aged from 54 to 76 years with chronic hepatic disease were included in this study. They all had cirrhosis of the liver (Table 2) which had been alcohol-induced in three cases.…”

Section: Introduction Methodsmentioning

confidence: 79%

“…There was little difference in the total amount of water, sodium, potassium and creatinine excreted in 24 h after oral and intravenous administration of bumetanide (Table 5) Marcantonio et al (1982) Xux = total amount of bumetanide excreted in urine in 30 h F = bioavailability *P < 0.05, ***P < 0.001 as compared with normal group was higher after oral than after intravenous administration (Table 5). This difference in response was statistically significant.…”

Section: Pharmacodynamicsmentioning

confidence: 98%

“…There have been a number of studies on the pharmacokinetics of bumetanide in normal subjects after either a single route of administration (Dixon et al, 1976;Pentikainen et al, 1980) or after intravenous and oral administration (Marcantonio et al, 1982). However, little is known about its pharmacokinetics in disease states.…”

Section: Introduction Methodsmentioning

confidence: 99%

“…-00 C~~n ormal subjects aged 22 to 36 years (Marcantonio et al, 1982) (Table 3). After oral ingestion of bumetanide (1 mg), 9.85 + 3.5% was excreted unchanged whilst 12.06 + 4.5% was excreted unchanged after intravenous administration.…”

Section: P~umentioning

confidence: 99%

“…The method by which the pharmacokinetic parameters were calculated is described elsewhere (Marcantonio et al, 1982 …”

Section: Serum and Urine Samplesmentioning

confidence: 99%

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The pharmacokinetics and pharmacodynamics of the diuretic bumetanide in hepatic and renal disease.

Marcantonio¹,

Auld²,

Murdoch³

et al. 1983

Brit J Clinical Pharma

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1Bumetanide (1 mg) was given orally and intravenously to a group of patients with chronic renal failure (n = 6) and to another group with cirrhosis of the liver (n = 8). 2 The pharmacokinetics, using a two-compartment model, and the pharmacodynamics of the drug in these patients were compared with those previously obtained for normal subjects. 3 In the renal group serum bumetanide concentrations were higher than for the normal subjects and the terminal half-lives were significantly prolonged (P < 0.001). A decreased whole body clearance was attributable to a low renal clearance of drug, the non-renal clearance being significantly increased (P < 0.01). 4 For the patients with liver disease, serum bumetanide concentrations were higher than for the renal group, and the terminal half-lives were significantly further prolonged (P < 0.001). Both non-renal and renal clearances were significantly reduced (P < 0.001). 5 Absorption rates were not significantly altered in either group and the values of F (bioavailability) were 0.82 and 0.95 for the patients with renal disease and hepatic disease, respectively. 6 A poor pharmacodynamic response and a reduced bumetanide excretion rate were observed for the patients with chronic renal failure, whereas with hepatic disease normal bumetanide excretion rates were observed with an impaired diuretic response.

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Section: Introduction Methodsmentioning

confidence: 79%

Section: Pharmacodynamicsmentioning

confidence: 98%

Section: Introduction Methodsmentioning

confidence: 99%

Section: P~umentioning

confidence: 99%

“…The method by which the pharmacokinetic parameters were calculated is described elsewhere (Marcantonio et al, 1982 …”

Section: Serum and Urine Samplesmentioning

confidence: 99%

See 3 more Smart Citations

The pharmacokinetics and pharmacodynamics of the diuretic bumetanide in hepatic and renal disease.

Marcantonio¹,

Auld²,

Murdoch³

et al. 1983

Brit J Clinical Pharma

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Application of a physiologically‐based pharmacokinetic model for the prediction of bumetanide plasma and brain concentrations in the neonate

Donovan

Abduljalil

Cryan

et al. 2018

Biopharm & Drug Disp

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Bumetanide is a loop diuretic that is proposed to possess a beneficial effect on disorders of the central nervous system, including neonatal seizures. Therefore, prediction of unbound bumetanide concentrations in the brain is relevant from a pharmacological prospective. A physiologically-based pharmacokinetic (PBPK) model was developed for the prediction of bumetanide disposition in plasma and brain in adult and paediatric populations. A compound file was built for bumetanide integrating physicochemical data and in vitro data. Bumetanide concentration profiles were simulated in both plasma and brain using the Simcyp PBPK model. Simulations of plasma bumetanide concentrations were compared against plasma levels published in the literature. The model performance was verified with data from adult studies before predictions in the paediatric population were undertaken. The adult and paediatric intravenous models predicted pharmacokinetic factors, namely area under the concentration-time curve, maximum concentration in plasma and time to maximum plasma concentration, within two-fold of observed values. However, predictions of plasma concentrations within the neonatal intravenous model did not produce a good fit with the observed values. The PBPK approach used in this study produced reasonable predictions of plasma concentrations of bumetanide, except in the critically ill neonatal population. This PBPK model requires more information regarding metabolic intrinsic clearance and transport parameters prior to further validation of drug disposition predictions in the neonatal population. Given the lack of information surrounding certain parameters in this special population, the model is not appropriately robust to support the recommendation of a suitable dose of bumetanide for use as an adjunct antiepileptic in neonates.

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Effects of phenobarbital and 3‐methylcholanthrene pretreatment on the pharmacokinetics and the pharmacodynamics of bumetanide in rats

Choi

Lee

Jang

et al. 1991

Biopharm & Drug Disp

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The effects of pretreatment with the enzyme inducers, phenobarbital (PB) and 3-methylcholanthrene (3-MC), on the pharmacokinetic and pharmacodynamic parameters of bumetanide were examined in rats. The nonrenal clearance (19.3 vs 29.6 ml min-1 per kg) of bumetanide increased significantly in PB treated rats. This suggested that the nonrenal metabolism of bumetanide is increased by pretreatment with PB, which was supported by significantly increased amounts of bumetanide glucuronide and desbutyl bumetanide excreted in 8-h urine, and reduced amounts of bumetanide remaining per gram of tissue after 30-min incubation of 100 micrograms of bumetanide with the 9000 xg supernatant fraction of liver, stomach, and kidney tissue homogenates in PB treated rats. The contents of hepatic cytochrome P-450 (1.29 vs 2.15 nmol mg-1 protein) and the weights of liver and stomach increased significantly in PB treated rats, suggesting that the metabolizing enzymes for bumetanide are induced by pretreatment with PB. The 8-h urine output per 100 g body weight was not significantly different by pretreatment with PB although the amounts of bumetanide excreted in 8-h urine increased significantly in PB treated rats. It could be explained by the fact that the dose of bumetanide used results in urinary concentrations at the plateau of the concentration-effect relationship. Therefore, the alteration in the urinary excretion rate of bumetanide by pretreatment with PB would not alter the diuretic effect. In 3-MC treated rats, pharmacokinetic and pharmacodynamic parameters were not significantly different and it suggested that the metabolizing enzymes for bumetanide are not induced by pretreatment with 3-MC although the contents of hepatic cytochrome P-450 and the weights of liver and stomach increased significantly by pretreatment with 3-MC.

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The pharmacokinetics and pharmacodynamics of bumetanide in normal subjects

Cited by 28 publications

References 12 publications

The pharmacokinetics and pharmacodynamics of the diuretic bumetanide in hepatic and renal disease.

The pharmacokinetics and pharmacodynamics of the diuretic bumetanide in hepatic and renal disease.

Application of a physiologically‐based pharmacokinetic model for the prediction of bumetanide plasma and brain concentrations in the neonate

Effects of phenobarbital and 3‐methylcholanthrene pretreatment on the pharmacokinetics and the pharmacodynamics of bumetanide in rats

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