Saline is as effective as nitrogen scavengers for treatment of hyperammonemia

Straten, Giora van; Velden, Monique G.M. de Sain–van der; Geijlswijk, Ingeborg M. van; Favier, Robert P.; Mesu, S. J.; Holwerda-Loof, N. E.; Ham, Maria van der; Fieten, Hille; Rothuizen, J.; Spee, Bart; Verhoeven‐Duif, Nanda M.

doi:10.1038/s41598-017-12686-9

Cited by 5 publications

(10 citation statements)

References 45 publications

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“…Elimination half-lives of SB and SPA were 2.7 and 2.4 hours, respectively. 18 These values are similar to those reported in humans. Both treatments were shown to have only mild adverse effects.…”

supporting

confidence: 87%

“…The doses and treatment protocol were equivalent to protocols used in humans 23 and a study evaluating the efficacy and safety of IV SB and SPA in dogs. 18…”

Section: Methodsmentioning

confidence: 99%

“…Both SB and SPA were reported to lower blood ammonia concentrations by providing alternative pathways for nitrogen excretion (Figure ). In dogs, benzoate and phenylacetate form conjugates with glycine to form hippuric acid (HA) and phenylacetylglycine (PAG), respectively . Both HA and PAG are excreted by the kidneys, thereby each removing 1 mole of nitrogen for every mole of SB and SPA administered …”

Section: Introductionmentioning

confidence: 99%

“…In a recent study, the efficacy and safety of IV SB and SPA were evaluated in healthy and CPSS dogs. Elimination half‐lives of SB and SPA were 2.7 and 2.4 hours, respectively . These values are similar to those reported in humans.…”

Section: Introductionmentioning

confidence: 99%

“…In dogs, benzoate and phenylacetate form conjugates with glycine to form hippuric acid (HA) and phenylacetylglycine (PAG), respectively. [18][19][20] Both HA and PAG are excreted by the kidneys, thereby each removing 1 mole of nitrogen for every mole of SB and SPA administered. 21,22 In a recent study, 18 the efficacy and safety of IV SB and SPA were evaluated in healthy and CPSS dogs.…”

mentioning

confidence: 99%

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Efficacy of orally administered sodium benzoate and sodium phenylbutyrate in dogs with congenital portosystemic shunts

Straten

Dalen

Mesu

et al. 2019

Veterinary Internal Medicne

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Background Hyperammonemia can result in hepatic encephalopathy, which in severe cases eventually can lead to coma and death. In dogs, congenital portosystemic shunts (CPSS) are the most common cause for hyperammonemia. Conservative treatment consists of a protein modified diet, nonabsorbable disaccharides, antibiotics, or some combinations of these. Sodium benzoate (SB) and sodium phenylbutyrate (SPB) both are used in the acute and long‐term treatment of humans with hyperammonemia caused by urea cycle enzyme deficiencies. Both treatments are believed to lower blood ammonia concentrations by promoting excretion of excess nitrogen via alternative pathways. Objectives To evaluate the efficacy and safety of PO treatment with SB and SPB on hyperammonemia and clinical signs in CPSS dogs. Methods Randomized, double‐blind, placebo‐controlled crossover trial. Concentrations of blood ammonia and bile acids were measured in CPSS dogs before and after a 5‐day treatment with SB, SPB, and placebo. A wash‐out period of 3 days was used between treatments. A standard questionnaire was developed and distributed to owners to evaluate clinical signs before and after each treatment. Results Blood ammonia concentrations were not influenced by any of the treatments and were comparable to those observed during placebo treatment. In addition, SB and SPB treatment did not result in improvement of clinical signs. Adverse effects during treatment included anorexia, vomiting, and lethargy. Conclusions and Clinical Importance Based on our results, we conclude that SB or SPB are not useful in the conservative treatment of hyperammonemia in dogs with CPSS.

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supporting

confidence: 87%

“…The doses and treatment protocol were equivalent to protocols used in humans 23 and a study evaluating the efficacy and safety of IV SB and SPA in dogs. 18…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Efficacy of orally administered sodium benzoate and sodium phenylbutyrate in dogs with congenital portosystemic shunts

Straten

Dalen

Mesu

et al. 2019

Veterinary Internal Medicne

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Intravenous and Oral Hyperammonemia Management

Alshaya

Fanikos

DeMaio

2018

Curr Emerg Hosp Med Rep

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Exposures of Phenylacetic Acid and Phenylacetylglutamine Across Different Subpopulations and Correlation with Adverse Events

et al. 2021

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Background Elevated plasma ammonia is central to the pathogenesis of hepatic encephalopathy. Sodium phenylacetate or glycerol phenylbutyrate is approved for urea cycle disorders, but limited clinical data are available for hepatic encephalopathy. Phenylacetic acid (PAA) plasma exposure has been reported to correlate with neurologic adverse events in patients with cancer but not in patients with urea cycle disorders or hepatic encephalopathy. Ornithine phenylacetate, an intravenous dosage form of the l-ornithine salt of phenylacetate, is under development for hepatic encephalopathy. Objective This analysis summarized the pharmacokinetics and safety of ornithine phenylacetate to support the dosing strategy and to assist with the monitoring and management of neurologic adverse events in a global clinical development program. Methods Phenylacetic acid and phenylacetylglutamine (PAGN) pharmacokinetic data and adverse events from five clinical studies were included in the analysis. Hepatic and renal dysfunction were assessed by baseline Child-Pugh score and creatinine clearance, respectively. Predicted plasma exposures of PAA at the occurrence of neurologic adverse events were used for exposures and neurologic adverse event analysis. Results Phenylacetic acid exhibited nonlinear pharmacokinetics. Phenylacetic acid exposure was 35% higher in Child-Pugh C than in Child-Pugh B. No significant pharmacokinetic difference was identified between Caucasian and Asian subjects after body weight adjustment. Phenylacetylglutamine renal clearance decreased by five-fold in severe renal impairment compared with subjects with normal renal function. Renal dysfunction significantly elevated PAGN plasma concentrations; however, elevated PAGN due to reduced excretion of PAGN did not change PAA exposure and plasma ammonia levels. No correlation was observed between PAA plasma exposure and neurologic adverse events in patients with stable cirrhosis or acute hepatic encephalopathy. Conclusions Dose adjustment should be considered for patients with low body weight and severely impaired hepatic function. Phenylacetic acid plasma exposure was not correlated with neurologic adverse events in the ornithine phenylacetate target patient population.

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Saline is as effective as nitrogen scavengers for treatment of hyperammonemia

Cited by 5 publications

References 45 publications

Efficacy of orally administered sodium benzoate and sodium phenylbutyrate in dogs with congenital portosystemic shunts

Efficacy of orally administered sodium benzoate and sodium phenylbutyrate in dogs with congenital portosystemic shunts

Intravenous and Oral Hyperammonemia Management

Exposures of Phenylacetic Acid and Phenylacetylglutamine Across Different Subpopulations and Correlation with Adverse Events

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