Bioavailability and disposition of 3H-solanine in rat and hamster.
1. The toxicokinetics of [3H]-alpha-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 micrograms/kg; the oral dose was 170 micrograms/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 alpha-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 alpha-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 alpha-solanine is only 1.6 and 3.2%, respectively, when compared with i.v. administration. 4. T1/2el of alpha-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 alpha-solanine than the rat.
Groen
K
K
Unit of Biotransformation, Pharmaco- and Toxicokinetics, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Pereboom-de Fauw
D P
DP
Besamusca
P
P
Beekhof
P K
PK
Speijers
G J
GJ
Derks
H J
HJ
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002240:Carbohydrate Sequence; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry; D007275:Injections, Intravenous; D008297:Male; D008647:Mesocricetus; D008969:Molecular Sequence Data; D051381:Rats; D012992:Solanine / Q000493:pharmacokinetics* / Q000633:toxicity*; D013045:Species Specificity; D014316:Tritium
D014316:Tritium; D012992:Solanine