Metabolism of garlic constituents in the isolated perfused rat liver.

The metabolic and kinetic behaviour of different garlic (Allium sativum L., Alliaceae) constituents were investigated in the isolated perfused rat liver, using aqueous extracts of garlic powder as well as isolated allicin, the main product of the enzymatic degradation of alliin. Allicin (allyl thiosulfinate) showed a remarkable first pass effect and passed the liver unmetabolized only at high concentrations which caused considerable cell injuries. Diallyl disulfide and allyl mercaptan were identified as metabolites of allicin, whereby diallyl disulfide probably is the metabolic precursor of allyl mercaptan as shown by perfusion with diallyl disulfide alone. The metabolites diallyl disulfide and allyl mercaptan could be determined in the perfusion medium as well as in the bile and the liver tissue. Other degradation products of garlic were also investigated in this model. Ajoenes and vinyldithiins were detected in perfusion medium after liver passage but no metabolites of them could be identified up to now.

Pharmacokinetics of vinyldithiins, transformation products of allicin.

The pharmacokinetic behaviour of vinyldithiins, the main constituents of oily preparations of garlic (Allium sativum L.), was investigated after oral administration of 27 mg 2-vinyl-4H-1,3-dithiin and 9 mg 3-vinyl-4H-1,2-dithiin to rats. In serum, kidney, and fat tissue, both vinyldithiins could be detected by GC-MS over a period of 24 h, whereas in liver only 1,3-vinyldithiin was found. Pharmacokinetic parameters (t1/2, ke, Cltot, AUC, and Vd) were determined using compartment models, elucidating the different pharmacokinetic behaviour of both vinyldithiins. 1,3-Vinyldithiin seems to be less lipophilic and is rapidly eliminated from serum, kidney, and fat tissue, whereas 1,2-vinyldithiin is more lipophilic and shows a tendency to accumulate in fat tissue. Experiments with liver homogenate confirmed the in vivo findings on the different degradation rates of both vinyldithiins. Allicin, the precursor of the vinyldithiins, is metabolized more rapidly in liver homogenate than the vinyldithiins.