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

  title={Pharmacokinetics, metabolism, and excretion of nefopam, a dual reuptake inhibitor in healthy male volunteers},
  author={Madhu Sanga and John A. Banach and Aaron R. Ledvina and Nishit B Modi and Aravind Mittur},
  pages={1001 - 1016}
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 [14C]-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… 
An open-label, single-dose, phase 1 study of the absorption, metabolism and excretion of quizartinib, a highly selective and potent FLT3 tyrosine kinase inhibitor, in healthy male subjects, for the treatment of acute myeloid leukemia
This study indicated that quizartinib was rapidly and orally bioavailable, extensively metabolized, with AC886 as the major circulating metabolite, and predominantly eliminated in faeces.
A Simultaneous Mixed-Effects Pharmacokinetic Model for Nefopam, N-desmethylnefopam, and Nefopam N-Oxide in Human Plasma and Urine
  • A. Mittur
  • Medicine, Chemistry
    European Journal of Drug Metabolism and Pharmacokinetics
  • 2017
A descriptive, robust and predictive parent–metabolite model has been developed using a population mixed-effects approach to characterize the pharmacokinetics of nefopam and its metabolites simultaneously in healthy subjects following oral administration of ne fopam.
Nefopam induced dose-related changes in renal and hepatic functions
Liver enzyme changes re lected and supported the histopathological indings in the liver tissue and Nefopam is well tolerable by the liver at low analgesic doses but may have detrimental effects at higher analgesics doses and prolonged duration of intake.
Comparison of oral and intravenous nefopam for fracture pain in Emergencies, Antananarivo
Oral ne fopam seems to be more efficient comparing to intravenous nefopam in fracture pain management in emergency room, and this practice should be implemented in emergency multimodal analgesia by its ease and efficiency of use.
Comparison Between Preoperative and Intraoperative Administration of Nefopam for Acute and Chronic Postoperative Pain in Colon Cancer Patients: A Prospective, Randomized, Double-Blind Study
Preoperatively administered nefopam reduced exertional pain compared to intraoperative administration although postoperative analgesic consumption was similar between two groups and it may be helpful to conduct early ambulation and deep breathing during the acute postoperative period in patients undergoing intestinal surgery.
The first synthesis of benzo[e]cycloalk[g]oxazocinone atropisomers via lactonization of N-mesyl- or N-arylsulfonyl-N-[2-(1-cycloalken-1-yl)-6-methylphenyl]glycines
Abstract The article describes an efficient access to cycloalkene-annulated benzoxazocines displaying both axial and central chiralities, via a domino halogenation-lactonization reaction of
MetaQSAR: An Integrated Database Engine to Manage and Analyze Metabolic Data.
The MetaQSAR tool is described, a new database engine specifically tailored to collect and analyze metabolic data, which takes advantage from all cheminformatics features implemented in the software with additional tools aimed to perform statistical analyses, similarity searches, and physicochemical profiling of the stored molecules.


Comparative pharmacokinetics and pharmacodynamics of intravenous and oral nefopam in healthy volunteers.
It is suggested that in healthy volunteers desmethyl-nefopam may contribute to the pharmacodynamic effects of single dose neFopam solution administered orally, and a rather low bioavailability of nefop am given in intravenous solution when administered orally is shown.
Effect of Route of Administration on the Pharmacokinetic Behavior of Enantiomers of Nefopam and Desmethylnefopam
This study shows that desmethylnefopam enantiomers can contribute to the analgesic effect of racemic ne fopam only when it is administered orally.
Nefopam Pharmacokinetics in Patients with End-Stage Renal Disease
Nefopam distribution and elimination are altered in patients with end-stage renal disease, resulting in heightened exposure and it is suggested that the daily nefopam dose be reduced by 50%.
Stereoselective demethylation of the enantiomers of nefopam, an experimental antidepressant and skeletal muscle relaxant.
Kinetic analysis of the demethylation of nefopam isomers by rat liver indicated that both isomers were demethylated by the same enzyme system, which indicated stereoselective metabolism of the drug.
Nefopam: A Review of its Pharmacological Properties and Therapeutic Efficacy
Nefopam is a non-narcotic analgesic not structurally related to other analgesic drugs, and when appropriate dose ratios were compared in short term studies it was shown to produce analgesia comparable to that with the oral analgesics aspirin, dextropropoxyphene and pentazocine, as well as that with ‘moderate’ doses of parenteral morphine, pethidine and pentacine.
Role of catecholamines and serotonin receptor subtypes in nefopam-induced antinociception.
Subcutaneous nefopam administration dose-dependently inhibited pain in acetic acid-induced writhing and formalin tests in the mouse and modulated by the adrenergic alpha(1) and alpha(2) receptors, the dopaminergic D(2%) receptors, and the serotonergic 5- HT(1B) and 5-HT(2C) receptor subtypes.
Drug metabolite concentration-time profiles: influence of route of drug administration.
The influence of route of drug administration on metabolite kinetics has been investigated by computer simulation and Comparisons between simulated profiles and published concentration-time data have been carried out.
Nefopam and Ketamine Comparably Enhance Postoperative Analgesia
Tachycardia and profuse sweating were more frequent in patients given nefopam, and sedation was more intense with ketamine; however, the incidence of other potential complications did not differ among groups.
Involvement of central serotonergic pathways in nefopam-induced antinociception.
The data suggest that descending serotonergic pathways are involved in nefopam-induced antinociception, as well as p-chlorophenylalanine (PCPA) pretreatment, which is not affected by PCA pretreatment.
Nefopam for the prevention of postoperative pain: quantitative systematic review.
There is limited evidence from the published literature that nefopam may be a useful non-opioid analgesic in surgical patients, and the analgesic potency seems to be similar to non-steroidal anti-inflammatory drugs.