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 (40.26 mu mol), the half-life (t(1/2)) 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 72 h. Similarly, in PM subjects t(1/2) = 6.5 +/- 0.9 h and recovery 89.9 +/- 4.5%.3. For orally administered 13-hydroxylupanine (37.83 (mu mol) the t(1/2) in FM subjects was 6.8+/-1.0 h with a recovery of 100.5 +/- 5.3%, and in PM subjects t(1/2) = 5.9 +/- 1.6 h with a recovery of 102.5 +/- 4.8%.4. The t(1/2)s 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 t(1/2)s 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.
|Journal||Xenobiotica: the fate of foreign compounds in biological systems|
|Publication status||Published - 1994|
Petterson, D. S., Grierson, B. N., Allen, D. G., Harris, D. J., Power, B. M., Dusci, L. J., & Ilett, K. (1994). Disposition of lupanine and 13-hydroxylupanine in man. Xenobiotica: the fate of foreign compounds in biological systems, 24, 933-941. https://doi.org/10.3109/00498259409043291