Disposition of lupanine and 13-hydroxylupanine in man.
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 mumol), 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 72 h. Similarly, in PM subjects t1/2 = 6.5 +/- 0.9 h and recovery 89.9 +/- 4.5%. 3. For orally administered 13-hydroxylupanine (37.83 mumol) 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 +/- 1.6 h 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.
Petterson
D S
DS
Department of Agriculture, Baron-Hay Court, South Perth, Australia.
Greirson
B N
BN
Allen
D G
DG
Harris
D J
DJ
Power
B M
BM
Dusci
L J
LJ
Ilett
K F
KF
D000470:Alkaloids / Q000378:metabolism* / Q000494:pharmacology; D001772:Blood Cell Count / Q000187:drug effects; D001774:Blood Chemical Analysis; D001794:Blood Pressure / Q000187:drug effects; D005410:Flame Ionization; D008401:Gas Chromatography-Mass Spectrometry; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D010641:Phenotype; D013034:Sparteine / Q000031:analogs & derivatives
D000470:Alkaloids; C091205:13-hydroxylupanine; C008298:lupanine; D013034:Sparteine