STUDIES ON THE PHARMACOKINETICS OF THE S- 35 LABELED GARLIC CONSTITUENTS ALLIIN, ALLICIN, AND VINYLDITHIINES

Studies on the Pharmacokinetics of the S-35-labeled Garlic Constituent s Alliin, Allicin and Vinyldithiines Three groups of 3 rats received o ral doses (8 mg/kg) of garlic constituents (alliin, allicin and vinyld ithiines (2-vinyl-[4H]-1,3-dithiine and 3-vinyl-[4H]-1,2-dithiine)) in the form of an oil macerate of the S-35-labeled substance. The measur ed activity was referred to S-35-alliin (S-35-alliin equivalents). The blood activity levels in each group were monitored for 72 h. For S-35 -allicin and the labeled vinyldithiines the excretion with the urine, feces, and exhaled air was also measured. The distribution among the o rgans (whole-body autoradiography) and the urinary metabolite pattern (thin-layer chromatography) were also determined. For S-35-alliin the blood activity profile differed considerably from those of S-35-allici n and the labeled vinyldithiines: both the absorption and the eliminat ion of the radioactivity were distinctly faster than for the other gar lic constituents, maximum blood levels being reached within the first 10 min and elimination from the blood being almost complete after 6 h. For the other garlic constituents the maximum blood levels were not r eached until 30-60 min (S-35-allicin) or 120 min (vinyldithiines) p.a. and blood levels> 1000 ng-Eq/ml were still present at the end of the study after 72 h. The mean total urinary and fecal excretion after 72 h was 85.5% (S-35-allicin) or 92.3% (labeled vinyldithiines) of the do se. The urinary excretion indicates a minimum absorption rate of 65% ( S-35-allicin) or 73% (vinyldithiines). It is uncertain whether the 19- 21% recovered in the feces was unabsorbed substance or had been excret ed via the bile or intestinal mucosa. The exhaled air showed only trac es of activity although the whole-body autoradiographs, after fairly l ong exposure (96 h), showed distinct enrichment of activity in the muc osa of the airways and pharynx. The activity is deposit mainly in the cartilage of the vertebral column and ribs. There was no detectable di fference in organ distribution between S-35-allicin and the labeled vi nyldithiines. All that could be established from the urinary metabolit e pattern was that unchanged S-35-allicin and unchanged labeled vinyld ithiines are absent. There is therefore extensive metabolization. The metabolites must have a very polar structure with acid functional grou ps since satisfactory separation was achievable only with acid solvent systems. Conjugates with sulfuric or glucuronic acid ware not detecta ble. These results reveal no differences in pharmacokinetic behavior b etween S-35-allicin and the labeled vinyldithiines. A final verdict as to whether the metabolites, which may be pharmacologically active, ar e identical must await further studies designed to identify the metabo lites.