T. Hirota, K. Kawai, T. Tokui
1988
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Quality indicators
Journal
Drug Metabolism and Pharmacokinetics
Abstract
FO-1561 (S-adenosyl-L-methionine, disulfate, tosylate) labeled at three different positions with 14C([CH3-14C]FO-1561, [Met-2-14C]FO-1561 and [Ade-8-14C]FO-1561) was administered intravenously to dogs (10 mg as S-adenosyl-L-methionine (SAMe[/kg) to examine the blood and plasma levels, excretion of radioactivity and the plasma and urinary metabolites. Radioactive phosphatidylcholine in some tissues were also quantified after intravenous administration of [CH3-14C]FO-1561. The blood and plasma radioactivity rapidly decreased biphasically until 4 hour and no difference was observed in pharmacokinetic behavior among the three differently labeled FO-1561 compounds. HPLC analysis also showed that the radioactivity in the plasma until 2 hour was unchanged SAMe. More than 85 % of the administered radioactivity was excreted in the urine until 168 hour after administration of each type of labeled FO-1561. The excretion of radioactivity in feces was less than 5 % until 168 hour. Thus, the main excretory route was shown to be. renal excretion. Urinary metabolites were 5′-deoxy-5′-methylthioadenosine (MTA) and methionine after administration of [CH3-14C]FO-1561, homoserine, homoserine lactone and methionine after administration of [Met-2-14C]FO-1561, and MTA, adenine and S-adenosylhomocysteine after administration of [Ade-8-14C]FO-1561. However, unchanged SAMe accounted for more than 80 % in urine until 48 hour. The brain, liver and plasma contained radioactive phosphatidylcholine after administration of [CH3-14C]FO-1561. From these results, the following two major metabolic pathways of exgeneous SAMe was demonstrated: 1) cleavage of C-S bond in SAMe resulting in the formation of homoserine, homoserine lactone and MTA, 2) transmethylation of S-methyl group to endogenous methyl acceptors such as phosphatidylethanolamine.