DISPOSITION OF LUPANINE AND 13-HYDROXYLUPANINE IN MAN

1. The in vivo disposition of lupanine and 13-hydroxylupanine was stud ied in subjects identified as poor metabolizers (PM, n=4) and extensiv e 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 subject s was 6.2 +/- 0.5 h (mean +/- SEM) with 95.5+/-6.0% of the dose recove red 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-hydrox ylupanine (37.83 (mu mol) the t(1/2) in FM subjects was 6.8+/-1.0 h wi th 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 lupanin e and 13-hydroxylupanine respectively did not differ significantly bet ween EM and PM phenotypes. In addition, total recovery of dose for bot h alkaloids was similar between phenotypes. 5. In most subjects, >76% of lupanine and >85% of 13-hydroxylupanine was recovered as the unchan ged compound. Significant apparent partial dehydroxylation of 13-hydro xy-lupanine was observed in one EM (14% of dose) and one PM (34% of do se) subject. 6. Overall, the finding of a high urinary recovery of unc hanged lupanine or 13-hydroxylupanine together with similar t(1/2)s fo r both alkaloids in EM and PM CYP2D6 phenotypes suggests that clinical toxicity is unlikely to result from the use of lupin seed in footstuf fs.