Interindividual Variability of the Clinical Pharmacokinetics of Methadone

  title={Interindividual Variability of the Clinical Pharmacokinetics of Methadone},
  author={Chin B. Eap and Thierry Buclin and Pierre Baumann},
  journal={Clinical Pharmacokinetics},
Methadone is widely used for the treatment of opioid dependence. Although in most countries the drug is administered as a racemic mixture of (R)- and (S)-methadone, (R)-methadone accounts for most, if not all, of the opioid effects. Methadone can be detected in the blood 15–45 minutes after oral administration, with peak plasma concentration at 2.5–4 hours. Methadone has a mean bioavailability of around 75% (range 36–100%). Methadone is highly bound to plasma proteins, in particular to α1-acid… 
Interindividual Variability of Methadone Response
Genetic polymorphisms in genes coding for methadone-metabolizing enzymes, transporter proteins, and μ-opioid receptors may explain part of the observed interindividual variation in the pharmacokinetics and pharmacodynamics of methadon.
Pharmacokinetics of Methadone
General dosing guidelines, dosage conversions from other opioids and pharmacokinetic issues in Special populations are discussed and unique and clinically important elements of methadone disposition including its absorption profile, distribution, and metabolism/excretion are summarized.
Determination of the unbound fraction of R- and S-methadone in human brain
Small but statistically significant differences in median fu for the R-methadone enantiomer were identified between case-categories, but these are thought to be too low to be of any forensic value.
Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horses.
The PK profile of methadone was characterized by high clearance (Cl/F), small volume of distribution (V(d)/F) and short elimination half-life (t(1/2)) and the mean of the estimated t( 1/2) (SD) for each dose was 2.2.
Effects of Hemodialysis on Methadone Pharmacokinetics and QTc.
Reduced Methadone Clearance During Aromatase Inhibition
Overall, these data demonstrate a significant decrease in methadone clearance during coadministration of letrozole, consistent with decreased metabolism brought about by aromatase inhibition and suggests a broader role for this catalyst of endogenous steroid metabolism in xenobiotic drug disposition.
Variability of Plasma Methadone Concentration in Opiate Dependent Receiving Methadone: A Personalised Approach Towards Optimizing Dose
Methadone acts on the opioid receptors and produces many of the same effects of morphine and heroin, and has cross-tolerance with other opioid, including heroin and morphine and a long duration of effect.
Modeling Methadone Pharmacokinetics in Rats in Presence of P-glycoprotein Inhibitor Valspodar
Valspodar increased methamphetamineadone’s bioavailability as consequence of P-gp inhibition, which resulted in an increased analgesic effect of methadone, which was successfully modeled using a two-compartmental model with a linear elimination from the central compartment and a first-order absorption process with lag time.


Plasma concentrations of the enantiomers of methadone and therapeutic response in methadone maintenance treatment.
Pharmacokinetics of methadone and its primary metabolite in 20 opiate addicts
In a closed metabolic ward the pharmacokinetics of methadone and its primary metabolite (EDDP) were studied in 20 long-term opiate addicts, and a poor correlation was found between the methad one dose and the steady-state level and the body clearance.
Pharmacokinetics and pharmacodynamics of methadone in patients with chronic pain
The results suggest that only the free (unbound) fraction of methadone present in blood is extracted by the liver and that methdone can be classified as a low (hepatic)‐extraction drug.
Steady-state pharmacokinetics of methadone in opioid addicts
The slow clearance of this drug from the body confirms that daily dosing at steady-state is adequate to maintain effective plasma concentrations throughout the dosing interval, and estimates of the variance of methadone clearance and apparent volume of distribution are given.
Clinical Pharmacokinetics of Methadone
In treatment of severe cancer pain such adaptive changes in methadone pharmacodynamics and pharmacokinetics are best managed by a regimen involving a fixed dose but a flexible and patient‐controlled dosage interval.
Disposition of methadone in man after a single oral dose
The renal clearance of methadone indicates that the drug is partially reabsorbed by a pH‐dependent process, and demonstrates the importance of biotransformation and renal excretion as determinants of the disposition of Methadone in man.
Single dose pharmacokinetics and bioavailability of methadone in man studied with a stable isotope method
The data show that for a majority of these subjects the bioavailability was higher than 45%, the previously reported value, and the marked individual variation in methadone pharmacodynamics and kinetics require an individually optimized dosage regimen.
Methadone: a review of its pharmacokinetic/pharmacodynamic properties.
High-Dose Morphine and Methadone in Cancer Patients
  • J. Säwe
  • Medicine, Biology
    Clinical pharmacokinetics
  • 1986
The pharmacokinetic studies have confirmed the rationale for regular administration of oral morphine and methadone but have revealed marked interindividual differences in the kinetics and metabolism which must be considered when titrating the oral dose according to the individual patient’s need.
Pharmacokinetics of methadone in methadone maintenance treatment: Characterization of therapeutic failures
The appropriate treatment of this subgroup of patients on methadone treatment is not to increase the dose but to shorten the dosage intervals, as the smaller volume of distribution could lead to unacceptably high fluctuation of M in the central compartment, and withdrawal symptoms during the latter part of the dosage interval.