Preclinical Toxicology Studies with Acyclovir: Acute and Subchronic Tests

Tucker, Walter E.; Macklin, A. W.; Szot, R.J.; Johnston, R.E.; Elion, Gertrude B.; Miranda, Paulo de; Szczech, George M.

doi:10.1093/toxsci/3.6.573

Cited by 6 publications

(6 citation statements)

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“…Crystal formation in the kidney has been reported for a number of poorly soluble drugs in laboratory animals. 296 Histological examination of animals treated with acyclovir revealed crystal clefts in the collecting tubules and ducts in the papillae accompanied by focal tubular dilatation, tubular cell hyperplasia and interstitial inflammation and foreign body giant cell formation. Predisposing factors in humans are intravascular volume depletion, concomitant renal insufficiency and various metabolic derangements that change urinary pH to favor crystal precipitation.…”

Section: Crystal Deposition Crystalluriamentioning

confidence: 98%

Urinary Tract

Greaves

2012

Histopathology of Preclinical Toxicity Studies

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Section: Crystal Deposition Crystalluriamentioning

confidence: 98%

Urinary Tract

Greaves

2012

Histopathology of Preclinical Toxicity Studies

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“…9). These (10), quinolone antibiotics (1, 7), purine analogues (10,11), and adenine (3), are known to produce crystalluria, crystal deposition, and obstructive nephropathy when high doses are given in laboratory animals. Microcrystalluria (and frequently hematuria) has occurred following ciprofloxacin administration in animals and is dependent on the pH of the urine (7).…”

Section: Methodsmentioning

confidence: 99%

Urinary Tract Toxicity in Rats Following Administration of β3-Adrenoceptor Agonists

et al. 1999

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(carboxymethyl)phenoxy]ethyl)-N -(β-hydroxyphenethyl)ammonium chloride], are β3-adrenoceptor stimulants with selectivity for brown adipose tissue. ZD7144 is the hydrochloride salt of the S-enantiomer of the racemic amide ZD2079. They were developed as potential novel treatments for obesity and non-insulin-dependent diabetes mellitus. Male and female rats were dosed separately by gavage for a minimum of 28 days with 0, 10, 50, and 500 mg/kg/day of ZD7114 or with 0, 10, 30, and 150 mg/kg/day of ZD2079. Two further groups of male and female rats were dosed with 0 and 500 mg/kg/day of ZD7114 for 28 days and were then allowed a 6-wk, undosed withdrawal period. At high doses, both compounds caused urinary tract toxicity, which primarily affected the distal tubules and collecting ducts of the kidney via tubular necrosis. They also caused ureteric inflammation, cystitis, and accumulation of crystalline inclusions throughout the urinary tract. As a result of urinary tract toxicity, affected animals from one or both studies showed reduced red blood cell indices, lower platelet counts, and higher white cell counts. Blood chemistry revealed lower plasma concentrations of glucose (7.28

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“…232 The reasons for this lack of correlation were unclear, although evaluation of human clinical data is complicated by the widespread use of combination chemotherapy. 237 This does not seem to have occurred in patients at therapeutic doses. 233 Species and age differences in sensitivity to anticancer drugs in laboratory animals have also been reported.…”

Section: Drug-induced Changes In Laboratory Animalsmentioning

confidence: 99%

Male Genital Tract

Greaves

2012

Histopathology of Preclinical Toxicity Studies

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Preclinical Toxicology Studies with Acyclovir: Acute and Subchronic Tests

Cited by 6 publications

References 0 publications

Urinary Tract

Urinary Tract

Urinary Tract Toxicity in Rats Following Administration of β3-Adrenoceptor Agonists

Male Genital Tract

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