Clinical laboratory tests on laboratory animals during toxicity studies (Document D, Stage 3, Version 1).
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Biomedical subjects
Publications and source records attributed to J Nachbaur.
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Dazoxiben, an orally active specific inhibitor of thromboxane synthetase, was administered by mouth daily to dogs and rats for 6 months. Dogs showed no evidence of toxicity up to 300 mg day-1 kg-1, the highest dose level used. Rats showed no evidence of toxicity after 100 mg day-1 kg-1, but at 300 mg day-1 kg-1 there were slight increases in plasma calcium and urea concentrations and a moderate incidence of focal nephrosis; males showed a slightly increased platelet count. Studies in rats and rabbits at dose levels up to 400 mg day-1 kg-1, by mouth, revealed no adverse effects on male or female fertility, embryogenesis, parturition or postnatal development. As dazoxiben is well absorbed after oral administration, the generally negative outcome to these toxicity studies suggests that selective inhibitors of thromboxane synthesis may be largely free of adverse effects which might impede their therapeutic or prophylactic use in clinical medicine.
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Sodium, potassium, and chloride plasma levels were measured in 294 male and 286 female Sprague Dawley rats [Crl:COBS CD(SD)BR]. The rats were distributed between four groups according to age (65-125 days, 235-275 days, 353-482 days, and 665-775 days). The levels of all three ions were higher in males than in females: about 1% higher for sodium and chloride and about 7% higher for potassium. Potassium and chloride values decreased with increasing age in both sexes; potassium decreased 12% and chloride decreased 6%. Distributions were not perfectly Gaussian but the departures from normality were slight. It was concluded, therefore, that determinations based on parametric statistical tests on the data are unlikely to be seriously biased by the distribution.
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