Nitrofurantoin-Associated Lung and Liver Toxicity Leading to Liver Transplantation in a Middle-Aged Patient

Kiang, Tony K. L.; Ford, Jo‐Ann; Yoshida, Eric M.; Partovi, Nilufar

doi:10.4212/cjhp.v64i4.1039

Cited by 10 publications

(4 citation statements)

References 38 publications

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“…We selected PubMed Central database articles focusing on published cases of concomitant nitrofurantoin-induced lung and liver disease, including adults with a pulmonary evaluation and liver biopsy (Table 1 ) [ 9 , 13 , 14 , 15 , 16 , 17 , 18 ]. Data showed elderly women with prolonged nitrofurantoin use, where fatigue and respiratory symptoms (as dyspnea and dry cough) precede jaundice for weeks to months.…”

Section: Discussionmentioning

confidence: 99%

Concomitant Nitrofurantoin-Induced Autoimmune Hepatitis and Interstitial Lung Disease

Matos

Macedo

Mendes

et al. 2021

GE Port J Gastroenterol

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Antibiotics are known to cause adverse reactions, but multiple organ involvement associated with nonspecific symptoms can lead to a delay in diagnosis. A definitive correlation between each toxin and its effects is difficult to establish due to concomitant potential toxins in the circulation. This article highlights an uncommon case of concomitant nitrofurantoin-induced autoimmune hepatitis and lung fibrosis that fulfills the definitive clinical criteria for diagnosis, presenting histological, imagiological, and immunological evidence of nitrofurantoin-induced toxicity. It occurred in a 68-year-old woman with extended nitrofurantoin intake for urinary tract infection prophylaxis who presented with progressive exercise dyspnea and jaundice. Similar published cases are also reviewed in this article.

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Section: Discussionmentioning

confidence: 99%

Concomitant Nitrofurantoin-Induced Autoimmune Hepatitis and Interstitial Lung Disease

Matos

Macedo

Mendes

et al. 2021

GE Port J Gastroenterol

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“…NFT-induced liver injury is implicated as acute hepatitis, granulomatous reaction, cholestasis, autoimmune-mediated hepatitis and chronic active hepatitis, even resulting in fulminant liver failure and death (Akšamija et al, 2009;Kiang et al, 2011;Sargın et al, 2012;Sakaan et al, 2014;Sorin et al, 2016). Acute liver damage is rare and may occur days or weeks after exposure to NFT, causing the increased level of liver function enzymes and elevated percentage of eosinophils.…”

Section: Nitrofurantoinmentioning

confidence: 99%

Metabolic Activation and Hepatotoxicity of Furan-Containing Compounds

2022

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Furan-containing compounds are abundant in nature, of which many but not all have been found to be hepatotoxic and carcinogenic. The furan ring present in the chemical structures may be one of the domineering factors to bring about the toxic response resulting from the generation of reactive epoxide or cis-enedial intermediates which are of the potential to react with biomacromolecules. This review sets out to explore the relationship between the metabolic activation and hepatotoxicity of furan-containing compounds on the strength of scientific reports on several typical alkylated furans, synthetic pharmaceuticals and components extracted from herbal medicines. The pharmacological activities as well as concrete evidence of their liver injuries are described, and the potential toxic mechanisms were discussed partly based on our previous work. Efforts were made to understand the development of liver injury and seek solutions to prevention and interference of the adverse effects.

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“…While several hepatic adverse events associated with NFT exposure have been reported, there is still a large gap in understanding the relationship between NFT exposure, its disposition, and the occurrence of adverse events [ 12 ]. Individual factors, such as gender, advanced age, dosage regimen, and renal insufficiency, have been identified as increasing the risk of developing DILI, as well as the ineffectiveness of therapy [ 1 , 2 , 13 , 14 , 15 , 16 ]. Despite being on the market for almost 60 years, there are surprisingly few pharmacokinetics (PK) studies of NFT.…”

Section: Introductionmentioning

confidence: 99%

Development of a Physiologically Based Pharmacokinetic Model for Nitrofurantoin in Rabbits, Rats, and Humans

Sharma,

Burgers,

Beltman

2023

Pharmaceutics

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Nitrofurantoin (NFT) is a commonly used antibiotic for the treatment of urinary tract infections that can cause liver toxicity. Despite reports of hepatic adverse events associated with NFT exposure, there is still limited understanding of the interplay between NFT exposure, its disposition, and the risk of developing liver toxicity. In this study, we aim to develop a physiologically based pharmacokinetic (PBPK) model for NFT in three different species (rabbits, rats, and humans) that can be used as a standard tool for predicting drug-induced liver injury (DILI). We created several versions of the PBPK model using previously published kinetics data from rabbits, and integrated enterohepatic recirculation (EHR) using rat data. Our model showed that active tubular secretion and reabsorption in the kidney are critical in explaining the non-linear renal clearance and urine kinetics of NFT. We subsequently extrapolated the PBPK model to humans. Adapting the physiology to humans led to predictions consistent with human kinetics data, considering a low amount of NFT to be excreted into bile. Model simulations predicted that the liver of individuals with a moderate-to-severe glomerular filtration rate (GFR) is exposed to two-to-three-fold higher concentrations of NFT than individuals with a normal GFR, which coincided with a substantial reduction in the NFT urinary concentration. In conclusion, people with renal insufficiency may be at a higher risk of developing DILI due to NFT exposure, while at the same time having a suboptimal therapeutic effect with a high risk of drug resistance. Our PBPK model can in the future be used to predict NFT kinetics in individual patients on the basis of characteristics like age and GFR.

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Nitrofurantoin-Associated Lung and Liver Toxicity Leading to Liver Transplantation in a Middle-Aged Patient

Cited by 10 publications

References 38 publications

Concomitant Nitrofurantoin-Induced Autoimmune Hepatitis and Interstitial Lung Disease

Concomitant Nitrofurantoin-Induced Autoimmune Hepatitis and Interstitial Lung Disease

Metabolic Activation and Hepatotoxicity of Furan-Containing Compounds

Development of a Physiologically Based Pharmacokinetic Model for Nitrofurantoin in Rabbits, Rats, and Humans

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