Bioavailability and disposition of ‘H-solanine in rat and hamster

Abstract

1. The toxicokinetics of [³H]-α-solanine after oral (p.o.) and intravenous (i.v.) administration in rat and hamster were studied, in order to decide which is the most appropriate model in risk assessment studies. The i.v. Dose was 54 βg/kg; the oral dose was 170 βg/kg.

2. After i.v. Administration, the toxicokinetics of total radioactivity in blood were comparable in rat and hamster. However, the clearance of total radioactivity from plasma was more effective in rat than in hamster. The half-lives of distribution and of the terminal phase of unchanged α-solanine were not different between rat and hamster, whereas the systemic and metabolic clearance were, respectively, about 1.6 and 2.7 times higher in rat than in hamster. The clearance of unchanged α-solanine is more effective than of total radioactivity.

3. After p.o. Administration in rat and hamster, the mean bioavailability of total radioactivity is about 29 and 57%, respectively. The bioavailability of unchanged α-solanine is only 1.6 and 3.2%, respectively, when compared with i.v. administration.

4. T_1/2el of α-solanine after p.o. Administration was in rats a factor of four and in hamsters a factor of two shorter than after i.v. Administration. A strong retention of radioactivity was seen in the hamsters after p.o. Administration; only 40% of the dose was excreted within 7 days versus 90% in rat.

5. Based on these and toxicological data from literature, it was decided that the hamster is a more appropriate model in (sub) chronic toxicity studies with α-solanine than the rat.