Adequate substitution with electrolytes in toxicological testing of “loop” diuretics in the dog

Garthoff, Bernward; Hoffmann, K.; Luckhaus, G; Thurau, Klaus

doi:10.1016/0041-008x(82)90001-1

Cited by 14 publications

(11 citation statements)

References 5 publications

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“…The symptoms observed in long-term toxicity studies appear to be determined by the pharmacologically induced and otherwise "desired" loss of electrolytes and water. Similar effects have been reported for furosemide (28), ethacrynic acid (69), and recently bumetanide (60). Muzolimine had no embryotoxic, teratogenic, or mutagenic effects.…”

Section: Mutagenicity Studiessupporting

confidence: 69%

“…Similar effects were seen in only one animal treated with 0.3 mg/kg P.o., whose water consumption and, therefore, electrolyte intake were extremely low. Although these results indicate that electrolyte substitution via drinking solution was not sufficient to compensate for electrolyte and volume loss when doses of 3 mg/kg or more were used, the symptoms of the electrolyte deficiency were not as marked as in the subchronic study where electrolytes were not replaced (28). Adequate electrolyte substitution for doses greater than 1 mg/kg was achieved by adding sodium and potassium chloride to the diet.…”

Section: Subchronic and Chronic Toxicitymentioning

confidence: 57%

“…No clinical symptoms or changes in plasma urea and creatinine were found in the subchronic (13 weeks) toxicity study (28). No histopathologic findings in the kidney or alterations in the other parameters were present (28). At repeated doses of 4.8 mg/kg, muzolimine was tolerated by dogs; as in the other toxicity studies, there were no indications of organ damage.…”

Section: Subchronic and Chronic Toxicitymentioning

confidence: 85%

“…Adequate electrolyte substitution for doses greater than 1 mg/kg was achieved by adding sodium and potassium chloride to the diet. No clinical symptoms or changes in plasma urea and creatinine were found in the subchronic (13 weeks) toxicity study (28). No histopathologic findings in the kidney or alterations in the other parameters were present (28).…”

Section: Subchronic and Chronic Toxicitymentioning

confidence: 96%

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Muzolimine

Garthoff

Hanisch

1984

Cardiovascular Drug Reviews

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Section: Mutagenicity Studiessupporting

confidence: 69%

Section: Subchronic and Chronic Toxicitymentioning

confidence: 57%

Section: Subchronic and Chronic Toxicitymentioning

confidence: 85%

Section: Subchronic and Chronic Toxicitymentioning

confidence: 96%

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Muzolimine

Garthoff

Hanisch

1984

Cardiovascular Drug Reviews

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“…The disposition of aminoglycosides in the kidney reflects these pathological alterations. 234 Electrolyte and fluid replacement alleviated these effects again suggesting that they were secondary to excessive electrolyte and water loss rather than a primary cellular toxic effect of the drugs. 220,221 A number of other drugs including macrolide antibiotics, immunosuppressive drugs and some platinum compounds may produce a range of analogous changes in laboratory animals.…”

Section: Histopathology Of Renal Tubular Necrosismentioning

confidence: 98%

Urinary Tract

Greaves

2012

Histopathology of Preclinical Toxicity Studies

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Toxicology and carcinogenicity studies of diuretics in F344 rats and B6C3F1 mice 2. Furosemide

Bucher

Huff

Haseman

et al. 1990

J of Applied Toxicology

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Toxicology and carcinogenesis studies of furosemide, a widely used diuretic, were conducted by administering diets containing the drug to both sexes of F344 rats and B6C3F1 mice in 14-day, 13-week and 2-year studies. Deaths occurred among rats and mice receiving diets containing 46,000 ppm furosemide in 14-day studies, and animals given diets containing lower concentrations lost weight. No deaths were seen in 13-week studies using top concentrations ranging from 10,000 to 20,000 ppm, but animals at higher concentrations had lower weight gains than controls. Nephrosis in rats and mice was the only significant compound-related lesion observed in the prechronic studies. In 2-year studies, rats received diets containing 0, 350 or 700 ppm furosemide and mice received diets containing 0, 700 or 1400 ppm furosemide. Survival of dosed and control rats of both sexes and male mice was similar; survival of high-dose female mice was lower than controls. Nephropathy was increased in male rats and in male and female mice. In female mice, increased malignant tumors of the mammary gland were associated with furosemide administration. In male rats, marginal increases in tubular cell neoplasms of the kidney and in meningiomas of the brain were observed in dosed animals, but these were not considered to be related clearly to exposure to furosemide.

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Adequate substitution with electrolytes in toxicological testing of “loop” diuretics in the dog

Cited by 14 publications

References 5 publications

Muzolimine

Muzolimine

Urinary Tract

Toxicology and carcinogenicity studies of diuretics in F344 rats and B6C3F1 mice 2. Furosemide

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