Clinical Toxicology publishes peer-reviewed scientific research and clinical advances in clinical toxicology. The journal reflects the professional concerns and best scientific judgment of its sponsors, the American Academy of Clinical Toxicology

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The introduction of peripherally acting μ-opioid receptor antagonists (PAMORAs) for the treatment of opioid-induced constipation brought opportunity for improved health and quality of life for patients on long-term opioid therapy.

Constipation is a bothersome, common, and underrecognized adverse effect (AE) of long-term opioid therapy. PAMORAs offer treatment for this condition and can improve patient adherence to the prescribed opioid therapy. However, it is crucial to understand the pharmacokinetic differences between the PAMORAs to aid in AE monitoring and minimize potentially strong drug-drug interactions (DDIs).

The 3 PAMORAs on the US market indicated for treating opioid-induced constipation from long-term opioid use are methylnaltrexone, naldemedine, and naloxegol. Each agent is available as oral tablets, and methylnaltrexone is also available as a subcutaneous injection. PAMORAs work by inhibiting the action of opioids in the gastrointestinal tract by combining with μ-receptors, thereby decreasing the constipating effects of opioids without compromising the analgesic effects in the central nervous system. These medications do not interfere with analgesia or cause opioid withdrawal, as they cannot cross the blood-brain barrier (BBB), because of their increased efflux across the BBB, large chemical structure, lipid solubility, and/or reduced permeability.1 Despite their overlapping mechanisms of action, the 3 PAMORAs differ in their pharmacokinetic properties. These properties can be harnessed based on a patient’s concomitant medications to help mitigate the risk of clinically relevant DDIs. The article “Peripheral Opioid Receptor Antagonists for Opioid-Induced Constipation: A Primer on Pharmacokinetic Variabilities with a Focus on Drug Interactions,” evaluates the subtle pharmacokinetic differences among these PAMORAs.

Media Contact:

Larry Tyler

Managing Editor

Journal of Clinical Toxicology

Mail ID: jct@peerjournal.org

Whatsapp: +1-504-608-2390