Acute Renal Toxic Effect of Amiodarone in Rats

Morales, Ana Isabel; Barata, José Diogo; Bruges, Margarida; Arévalo, Miguel; Buitrago, José Manuel González de; Palma, Patrícia; Branco, Patrícia; Pérez‐Barriocanal, Fernando

doi:10.1034/j.1600-0773.2003.920107.x

Cited by 22 publications

(17 citation statements)

References 14 publications

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“…In kidneys, reduced CL CR was observed in amiodarone-administered animals. This result complies with the described impairment of kidney function during acute amiodarone therapy [36]. Nevertheless, a decreased glomerular filtration rate after administration of amiodarone was not associated with reduction of MTX CL R .…”

Section: Discussionsupporting

confidence: 90%

Amiodarone modulates pharmacokinetics of low‐dose methotrexate in rats

Fuksa

Brčáková

Cermanova

et al. 2008

Biopharm & Drug Disp

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Clinical studies of low-dose methotrexate (LDMTX) pharmacokinetics document increased plasma concentrations of MTX after co-administration of the drug with amiodarone or macrolide antibiotics. As drug-drug interactions may increase the toxicity of LDMTX, a rat model was used to follow renal and biliary elimination of MTX during its constant-rate i.v. infusion and concomitant single bolus i.v. injections of amiodarone or azithromycin. The mean steady-state plasma concentration of 1.7+/-0.1 micromol/l was reached and the total clearance achieved 17.7+/-1.0 ml/min/kg. Administration of amiodarone decreased the biliary clearance of MTX to 73% of the control values (p<0.05). Correspondingly, the total clearance decreased to 72% and plasma MTX concentrations were augmented to 2.5+/-0.4 micromol/l (p<0.05). Amiodarone-treated rats exhibited a 3.3-fold decrease in the renal clearance (p<0.05) of conjugated bilirubin, which was associated with its increased plasma concentration. In contrast, azithromycin did not alter any of the MTX pharmacokinetic parameters. In conclusion, this is the first report describing the impairment of MTX hepatic elimination during co-administration with amiodarone. This study also provides new insight into acute amiodarone-induced hyperbilirubinaemia, where increased bilirubin production and decreased renal clearance may contribute to this effect. Importantly, azithromycin seems to be a safe co-medication during LDMTX therapy.

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Section: Discussionsupporting

confidence: 90%

Amiodarone modulates pharmacokinetics of low‐dose methotrexate in rats

Fuksa

Brčáková

Cermanova

et al. 2008

Biopharm & Drug Disp

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“…Amiodarone, an iodine-rich antiarrhythmic agent, can cause both hypothyroidism and hyperthyroidism (125,126), as well as acute renal damage (127). As mentioned before, rifampicin can cause tubulointerstitial nephritis and hyperthyroidism (73).…”

Section: Drugs In Thyroid and Renal Diseasesmentioning

confidence: 99%

Thyroid dysfunction and kidney disease

Iglesias

Díez

2009

European Journal of Endocrinology

376

352

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Thyroid hormones (TH) are essential for an adequate growth and development of the kidney. Conversely, the kidney is not only an organ for metabolism and elimination of TH, but also a target organ of some of the iodothyronines' actions. Thyroid dysfunction causes remarkable changes in glomerular and tubular functions and electrolyte and water homeostasis. Hypothyroidism is accompanied by a decrease in glomerular filtration, hyponatremia, and an alteration of the ability for water excretion. Excessive levels of TH generate an increase in glomerular filtration rate and renal plasma flow. Renal disease, in turn, leads to significant changes in thyroid function. The association of different types of glomerulopathies with both hyper-and hypofunction of the thyroid has been reported. Less frequently, tubulointerstitial disease has been associated with functional thyroid disorders. Nephrotic syndrome is accompanied by changes in the concentrations of TH due primarily to loss of protein in the urine. Acute kidney injury and chronic kidney disease are accompanied by notable effects on the hypothalamus-pituitary-thyroid axis. The secretion of pituitary thyrotropin (TSH) is impaired in uremia. Contrary to other non-thyroidal chronic disease, in uraemic patients it is not unusual to observe the sick euthyroid syndrome with low serum triodothyronine (T 3 ) without elevation of reverse T 3 (rT 3 ). Some authors have reported associations between thyroid cancer and kidney tumors and each of these organs can develop metastases into the other. Finally, data from recent research suggest that TH, especially T 3 , can be considered as a marker for survival in patients with kidney disease.

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“…The amiodarone-induced inhibition of tacrolimus metabolism resulted in significantly lower doses of tacrolimus necessary to achieve proper therapeutic serum concentrations [3]. Much less is known about effects of tacrolimus on possible elevation of amiodarone concentration, which may be clinically important while both animal and observational studies suggested that amiodarone may cause renal impairment by reducing renal blood flow or inducing tubular alterations [4][5][6].…”

Section: Discussionmentioning

confidence: 99%

“…Several case reports have described QT interval prolongation after concomitant use of amiodarone and tacrolimus [2,3]. Also, amiodarone nephrotoxicity has been demonstrated in animal and observational studies [4][5][6]. We report a case of kidney allograft dysfunction possibly caused by amiodarone nephrotoxicity precipitated by tacrolimus.…”

Section: Introductionmentioning

confidence: 97%

Renal Allograft Dysfunction Possibly Caused by Amiodarone Nephrotoxicity: a Case-Report

Bašić‐Jukić¹,

Katalinic²,

Čorić³

et al. 2017

BANTAO Journal

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Amiodarone is a potent inhibitor of CYP3A4 and can increase serum concentrations of drugs that are substrates of this enzyme system. Immunosuppressive drugs are also metabolized through the cytochrome metabolic pathway what may lead to important drug-drug interactions. A 60-year-old female received her second allograft from the deceased donor and was treated with tacrolimus, mycophenolate mofetil and steroids. Amiodarone was introduced for treatment of paroxysmal atrial fibrillation four days after the transplantation. One month after the discharge she was readmitted to hospital for evaluation of the creeping creatinine. Biopsy showed borderline acute rejection. She received 3 boluses of 6-methilprednisolone but creatinine continued to rise. Repeated biopsy was without signs of rejection with mild interstitial fibrosis/tubular atrophy, mild global glomerulosclerosis and moderate arterial sclerosis. However, tubular vacuolization was prominent. After careful revision of her therapy we decided to replace amiodarone with sotalol. One week later her creatinine fell from 350 to 220 µmol/l and remained stable. This case illustrates possible amiodarone nephrotoxicity in a renal transplant recipient. We suggest that patients who need amiodarone in combination with tacrolimus be closely monitored by both cardiologists and nephrologists, with frequent determinations of tacrolimus trough levels and serum creatinine measurements.

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Acute Renal Toxic Effect of Amiodarone in Rats

Cited by 22 publications

References 14 publications

Amiodarone modulates pharmacokinetics of low‐dose methotrexate in rats

Amiodarone modulates pharmacokinetics of low‐dose methotrexate in rats

Thyroid dysfunction and kidney disease

Renal Allograft Dysfunction Possibly Caused by Amiodarone Nephrotoxicity: a Case-Report

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