BIOAVAILABILITY AND DISPOSITION OF H-3 SOLANINE IN RAT AND HAMSTER

1. The toxicokinetics of [H-3]-alpha-solanine after oral (p.o.) and in travenous (i.v.) administration in rat and hamster were studied, in or der to decide which is the most appropriate model in risk assessment s tudies. The i.v. dose was 54 mug/kg; the oral dose was 170 mug/kg. 2. After i.v. administration, the toxicokinetics of total radioactivity i n blood were comparable in rat and hamster. However, the clearance of total radioactivity from plasma was more effective in rat than in hams ter. The half-lives of distribution and of the terminal phase of uncha nged alpha-solanine were not different between rat and hamster, wherea s the systemic and metabolic clearance were, respectively, about 1.6 a nd 2.7 times higher in rat than in hamster. The clearance of unchanged alpha-solanine is more effective than of total radioactivity. 3. Afte r p.o. administration in rat and hamster, the mean bioavailability of total radioactivity is about 29 and 57%, respectively. The bioavailabi lity of unchanged alpha-solanine is only 1.6 and 3.2%, respectively, w hen compared with i.v. administration. 4. T1/2el of alpha-solanine aft er 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 retenti on 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 decide d that the hamster is a more appropriate model in (sub)-chronic toxici ty studies with alpha-solanine than the rat.