Pharmacokinetics, metabolism, and excretion of nefopam, a dual reuptake inhibitor in healthy male volunteers.

1.The disposition of nefopam, a serotonin-norepinephrine reuptake inhibitor, was characterized in eight healthy male volunteers following a single oral dose of 75mg [C-14]-nefopam (100 Ci). Blood, urine, and feces were sampled for 168 h post-dose.2.Mean (SD) maximum blood and plasma radioactivity concentrations were 359 +/- 34.2 and 638 +/- 64.7 ngEq free base/g, respectively, at 2 h post-dose. Recovery of radioactive dose was complete (mean 92.6%); a mean of 79.3% and 13.4% of the dose was recovered in urine and feces, respectively.3.Three main radioactive peaks were observed in plasma (metabolites M2 A-D, M61, and M63). Intact [C-14]-nefopam was less than 5% of the total radioactivity in plasma. In urine, the major metabolites were M63, M2 A-D, and M51 which accounted for 22.9%, 9.8%, and 8.1% of the dose, respectively. An unknown entity, M55, was the major metabolite in feces (4.6% of dose). Excretion of unchanged [C-14]-nefopam was minimal.