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Biobeschikbaarheid en kinetiek van solanine in ratten en hamsters

Synopsis

The toxicokinetics of [3H]-alpha-solanine after oral (po) and intravenous (iv) administration in rats and hamsters were studied, in order to decide which is the most appropriate model in risk assessment studies. The iv dose was 54 mug/kg; the oral dose was 170 mug/kg. After iv administration, the toxicokinetics of total radioactivity in blood were comparable in rats and hamsters. However, the clearance of total radioactivity from plasma was more effective in rats than in hamsters The half-lives of distribution and of the terminal phase of unchanged alpha-solanine were not different between rats and hamsters, whereas the systemic and the metabolic clearance were about 1.6 and 2.7 times higher in rats than in hamsters, respectively. The clearance of unchanged alpha-solanine is more effective than that of total radioactivity. After oral administration in rats and hamsters, the mean bioavailability of total radioactivity is about 29% and 57%, respectively, whereas the bioavailability of unchanged alpha-solanine is only 1.6% and 3.2%, respectively, when compared with iv administration. T1/2 el of alpha-solanine after oral administration was in rats a factor of four and in hamsters a factor of two shorter than after iv administration. A strong retention of radioactivity was seen in the hamsters after oral administration; only 40% of the dose was excreted within seven days vs 90% in rats. In some hamsters, severe damage of the duodenal wall was observed after oral administration. Based on these data, it was decided that the hamster is a more appropriate model in (sub)-chronic toxicity studies with alpha-solanine than the rat.

 

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