Abstract
1. The in vivo disposition of lupanine and 13-hydroxylupanine was studied in subjects identified as poor metabolizers (PM, n = 4) and extensive metabolizers (EM, n = 7) phenotypes for cytochrome P4502D6 (CYP2D6).
2. After oral administration (40.26μmol), the half-life (t1/2) of lupanine determined from urinary excretion rate studies in EM subjects was 6.2 ± 0.5 h (mean ± SEM) with 95.5 ± 6.0% of the dose recovered unchanged within 72h. Similarly, in PM subjects t1/2 = 6.5 ± 0.9h and recovery 89.9 ± 4.5%.
3. For orally administered 13-hydroxylupanine (37.83 μmol) the t1/2 in EM subjects was 6.8 ± 1.0 h with a recovery of 100.5 ± 5.3%, and in PM subjects t1/2 = 5.9 ± 1.6h with a recovery of 102.5 ± 4.8%.
4. The t1/2S of both lupanine and 13-hydroxylupanine respectively did not differ significantly between EM and PM phenotypes. In addition, total recovery of dose for both alkaloids was similar between phenotypes.
5. In most subjects, < 76% of lupanine and < 85% of 13-hydroxylupanine was recovered as the unchanged compound. Significant apparent partial dehydroxylation of 13-hydroxy-lupanine was observed in one EM (14% of dose) and one PM (34% of dose) subject.
6. Overall, the finding of a high urinary recovery of unchanged lupanine or 13-hydroxylupanine together with similar t1/2S for both alkaloids in EM and PM CYP2D6 phenotypes suggests that clinical toxicity is unlikely to result from the use of lupin seed in footstuffs.