Absorption, distribution, metabolism, and excretion of radiolabeled naldemedine in healthy subjects

  title={Absorption, distribution, metabolism, and excretion of radiolabeled naldemedine in healthy subjects},
  author={Shuichi Ohnishi and Kazuya Fukumura and Ryuji Kubota and Toshihiro Wajima},
  pages={1044 - 1053}
Abstract 1. Naldemedine is a peripherally acting μ-opioid receptor antagonist for the treatment of opioid-induced constipation. 2. This phase 1 study investigated the absorption, distribution, metabolism and excretion of naldemedine, following a single oral 2-mg dose of [oxadiazole-14C]-naldemedine or [carbonyl-14C]-naldemedine to 12 healthy adult male subjects. Pharmacokinetic assessments were performed on blood, urine and fecal samples collected at defined intervals. 3. Naldemedine was the… 
5 Citations
The Influence of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Naldemedine
Investigation of the pharmacokinetics and safety of a 0.2‐mg oral dose of naldemedine in subjects with renal impairment or hepatic impairment found it to be well tolerated, and reported adverse events were generally consistent with the known safety profile.
Clinical Drug-Drug Interaction Studies to Evaluate the Effects of a P-Glycoprotein Inhibitor, CYP3A Inhibitors, and a CYP3A Inducer on the Pharmacokinetics of Naldemedine in Healthy Subjects
Coadministration of naldemedine with a P-glycoprotein inhibitor or a strong/moderate CYP3A inhibitor increases naldemsine exposure; coadministration with a strong CYP 3A inducer decreases its exposure.
Naldemedine for the Use of Management of Opioid Induced Constipation.
Naldemedine is an FDA-approved, once-daily oral tablet that counteracts this side effect of opioid-induced constipation by antagonizing mu, kappa, and delta-opioid receptors and has been shown to be safe and effective.
Naldemedine: A New Option for OIBD
The available data suggest that naldemedine is a valid treatment option for OIBD, as it is a well-tolerated drug that alleviates constipation without affecting analgesia or causing symptoms of opioid withdrawal.
Opioid-Induced Constipation in Oncological Patients: New Strategies of Management
Traditional recommended therapies are appraised and compared with the latest pharmacological developments, and whether naloxegol is more efficacious by its comparison directly with first-line treatments, including laxatives is addressed.


Phase 1, Randomized, Double‐Blind, Placebo‐Controlled Studies on the Safety, Tolerability, and Pharmacokinetics of Naldemedine in Healthy Volunteers
Overall, naldemedine was rapidly absorbed, and no safety or tolerability issues were noted at the doses evaluated, and the incidence of adverse events was not dose dependent.
Spotlight on naldemedine in the treatment of opioid-induced constipation in adult patients with chronic noncancer pain: design, development, and place in therapy
Based on the available data, naldemedine appears to be an effective and safe drug for the treatment of OIC in adults with chronic noncancer pain.
Efficacy of Treatments for Opioid‐Induced Constipation: Systematic Review and Meta‐analysis
  • J. Nee, M. Zakari, +6 authors A. Lembo
  • Medicine
    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
  • 2018
Overall, &mgr;‐opioid–receptor antagonists, lubiprostone, and prucalopride were superior to placebo for the treatment of OIC, with a RR of failure to respond to therapy of 0.70 and an overall number needed to treat of 5 (95% CI, 4–7).
Opioid complications and side effects.
The role of opioids in the treatment of chronic pain is influenced by the fact that these potent analgesics are associated with a significant number of side effects and complications, and these phenomena are the focus of this review.
Management of common opioid-induced adverse effects.
Understanding the mechanism for opioid-induced nausea will aid in the selection of appropriate agents, and Physicians should minimize the development of constipation using prophylactic measures.
The prevalence, severity, and impact of opioid-induced bowel dysfunction: results of a US and European Patient Survey (PROBE 1).
OBD occurs frequently, despite the use of laxatives, in individuals taking daily oral opioids for chronic pain, and these gastrointestinal symptoms add to the burden already experienced by chronic pain patients, negatively impacting quality of life and, in some cases, affecting opioid treatment itself.
Management of opioid-induced constipation
  • D. Thorpe
  • Medicine
    Current pain and headache reports
  • 2001
A bowel clean-out is indicated for patients who have not had a bowel movement in more than 5 days and a regular regimen of senna and docusate is recommended to overcome opioid-induced constipation.
Laxatives Do Not Improve Symptoms of Opioid-Induced Constipation: Results of a Patient Survey
Use of laxatives to treat opioid-induced constipation is often ineffective and associated with side effects, and instead of relieving the burden of opioid- induced constipation, laxative use is associated with a negative impact.
Opioid-induced constipation: advances and clinical guidance
This review addresses the clinical presentation and diagnosis of opioid-induced constipation, barriers to its diagnosis, effects of opioids in the gastrointestinal tract, differential tolerance to opiates in different gastrointestinal organs, medications approved and in development for the treatment of opioids, and a proposed clinical management algorithm for treating opioid- induced constipation in patients with noncancer pain.
Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid‐induced constipation
The mechanism of opioid‐induced constipation differs from that of functional constipation (FC), and OIC may not respond as well to most first‐line treatments for FC.