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Methadone Recycling Sustains Drug Reservoir in Tissue
Journal of Pain & Palliative Care Pharmacotherapy
|September 15, 2015
Summary
Scientists discovered a significant, quantifiable tissue store of methadone in humans. This tissue reservoir, larger than plasma levels, explains how methadone is sustained and recycled in the body.
Area of Science:
- Pharmacology
- Pharmacokinetics
- Human Physiology
Background:
- Methadone is a widely used opioid agonist.
- Its pharmacokinetic profile, particularly tissue distribution and recycling, is not fully understood.
- Understanding methadone tissue storage is crucial for optimizing treatment and managing side effects.
Purpose of the Study:
- To investigate the existence and quantify human tissue stores of methadone.
- To elucidate the mechanism of methadone tissue uptake, storage, and release (recycling).
- To determine the contribution of tissue stores to plasma methadone levels.
Main Methods:
- Clinical trial simulation using in silico pharmacokinetic modeling.
- Study involved a random sample of six opioid-naïve healthy subjects.
- Analysis of methadone levels in accessible and inaccessible compartments.
Main Results:
- A large, quantifiable methadone tissue store (13-17 mg) was identified, exceeding plasma concentrations after a single 10 mg oral dose.
- Methadone undergoes recycling 2-5 times between accessible (plasma) and inaccessible extravascular compartments.
- Estimated methadone tissue accumulation rate ranged from 0.029-7.29 mg/h, with 39-83% of tissue stores spilling over into circulation.
Conclusions:
- Humans possess substantial, quantifiable methadone tissue stores.
- Methadone exhibits a recycling mechanism involving tissue uptake, storage, and release.
- These tissue stores significantly contribute to maintaining plasma methadone levels in humans.
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