Synthesis of 14C-meglumine salicylate and its disposition in humans after oral administration

The synthesis of 14C-meglumine salicylate was accomplished by heating 14C-meglumine with salicylic acid, in equimolar ratios, in 2-propanol. The average radiochemical yield was 97.5%. Ten healthy adult male volunteers were given 1.2 g of the compound orally. Five took 1.2 g of 1-deoxy-1-[14C]-methylamino-D-glucitol salicylate (containing about 47 micronCi), and five others took 1.2 g of 1-deoxy-1-methylamino-D-[U-14 micronCi), and five others took 1.2 g of 1-deoxy-1-methylamino-D-[U-14C]-glucitol salicylate (containing about 45 micronCi). Urine and feces were collected for 5 days, and blood was sampled for 24 hr. The peak urinary excretion of meglumine and/or its metabolites occurred between 4 and 8 hr after administration (about 7.2% of the administered dose). Meglumine was excreted primarily in the feces (72.4% over 5 days) and, to a smaller extent, in urine (21.3% over 5 days). No activity was detected in blood. The excretion rate and percentage excreted were the same for both groups of subjects, suggesting that meglumine was not metabolized by N-demethylation or conversion to carbon dioxide. The highest blood salicylate level, 44.4 +/- 1.9 microng/ml, was observed 1 hr after administration. Urinary levels of salicylic acid and its metabolites were observed to be at a maximum at 8 hr. Total salicylate recovery was 94.7 +/- 1.5% in 48 hr. Salicyluric acid was the major metabolite, accounting for 69.5 +/- 3.6% of the dose. Salicylic acid accounted for 6.8 +/- 1.2%.