title: Pharmacokinetics, metabolism, and excretion of nefopam, a dual reuptake inhibitor in healthy male volunteers.
abstract: 1. The disposition of nefopam, a serotonin-norepinephrine reuptake inhibitor, was characterized in eight healthy male volunteers following a single oral dose of 75 mg [(14)C]-nefopam (100 μCi). 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 [(14)C]-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 [(14)C]-nefopam was minimal.
authors.affiliation: a Covance Laboratories Inc , Madison , WI , USA and.
authors.forename: Madhu
authors.initials: M
authors.lastname: Sanga
authors.affiliation: a Covance Laboratories Inc , Madison , WI , USA and.
authors.forename: John
authors.initials: J
authors.lastname: Banach
authors.affiliation: a Covance Laboratories Inc , Madison , WI , USA and.
authors.forename: Aaron
authors.initials: A
authors.lastname: Ledvina
authors.affiliation: b Department of Clinical Pharmacology , Impax Specialty Pharma (A Division of Impax Laboratories, Inc.) , Hayward , CA , USA.
authors.forename: Nishit B
authors.initials: NB
authors.lastname: Modi
authors.affiliation: b Department of Clinical Pharmacology , Impax Specialty Pharma (A Division of Impax Laboratories, Inc.) , Hayward , CA , USA.
authors.forename: Aravind
authors.initials: A
authors.lastname: Mittur
mesh_terms: D000284:Administration, Oral; D001692:Biological Transport; D005243:Feces / Q000737:chemistry; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D009340:Nefopam / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D009340:Nefopam; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Human disposition; mass balance; metabolite profiling and identification; radiolabeled nefopam