Variability of Plasma Methadone Concentration in Opiate Dependent Receiving Methadone: A Personalised Approach Towards Optimizing Dose

Mohamad, Nasir; Bakar, Nor Hidayah Abu; Choon, Tan Soo; Liang, Sim Hann; Nazar, Nim; Idrus, Ilya Irinaz; Ismail, Rusli

doi:10.5772/29620

Cited by 2 publications

(3 citation statements)

References 32 publications

(23 reference statements)

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“…Studies have demonstrated methadone detection and effects in the nervous system, therefore, the amount of methadone the nervous system is exposed to in a therapeutic regimen is important in determining the effects on a patient (Johnson & Rosecrans, ; Pertschuk, Ford & Rainford, ). This model incorporates the plasma protein binding of methadone, which is important as the therapeutic effects of methadone protein binding are well noted (Abramson, ; Garrido et al., ; Mohamad et al., ; Szeto, Umans, Umans & McFarland, ; Wilkins et al., ). Brain tissue concentrations are also important when looking at potential respiratory depression due to methadone, an important side effect when constructing therapeutic regimens.…”

Section: Discussionmentioning

confidence: 99%

The construction and application of a population physiologically based pharmacokinetic model for methadone in Beagles and Greyhounds

Elwell-Cuddy

KuKanich

Lin

2018

Vet Pharm & Therapeutics

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Methadone is an opioid analgesic in veterinary and human medicine. To help develop appropriate pain management practices and to develop a quantitative model for predicting methadone dosimetry, a flow-limited multiroute physiologically based pharmacokinetic (PBPK) model for methadone in dogs constructed with Berkeley Madonna™ was developed. The model accounts for intravenous (IV), subcutaneous (SC), and oral administrations, and compartmentalizes the body into different components. This model was calibrated from plasma pharmacokinetic data after IV administration of methadone in Beagles and Greyhounds. The calibrated model was evaluated with independent data in both breeds of dogs. One advantage of this model is that most physiological parameter values for Greyhounds were taken directly from the original literature. The developed model simulates available pharmacokinetic data for plasma concentrations well for both breeds. After conducting regression analysis, all simulated datasets produced an R > 0.80 when compared to the measured plasma concentrations. Comparative analysis of the dosimetry of methadone between the breeds suggested that Greyhounds had ~50% lower 24-hr area under the curve (AUC) of plasma or brain concentrations than in Beagles. Furthermore, population analysis was conducted with this study. This model can be used to predict methadone concentrations in multiple dog breeds using breed-specific parameters.

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Section: Discussionmentioning

confidence: 99%

The construction and application of a population physiologically based pharmacokinetic model for methadone in Beagles and Greyhounds

Elwell-Cuddy

KuKanich

Lin

2018

Vet Pharm & Therapeutics

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“…In the study described here, morphine, methadone, and cocaine (Figure ) were used as test cases for small-molecule detection in a novel, direct-detection primary antibody immunoassay. Cocaine is a narcotic, while methadone and morphine are both opioids which are known to bind to μ-opioid receptors . These small-molecules are well-known drugs with extensively documented histories of use for both pharmaceutical and recreational purposes. − All three of these drugs act upon the central nervous system and are highly addictive .…”

Section: Introductionmentioning

confidence: 99%

“…Cocaine is a narcotic, while methadone and morphine are both opioids which are known to bind to μopioid receptors. 8 These small-molecules are well-known drugs with extensively documented histories of use for both pharmaceutical and recreational purposes. 9−11 All three of these drugs act upon the central nervous system and are highly addictive.…”

Section: ■ Introductionmentioning

confidence: 99%

Revealing the Kinetic Advantage of a Competitive Small-Molecule Immunoassay by Direct Detection

2020

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Small-molecule detection in an immunoassay format generally employs competition or labeling. A novel direct-detection label-free primary immunoassay utilizing second harmonic generation (SHG) has been developed and the utility of the method has been demonstrated for several small-molecule narcotics. Specifically, the binding of morphine, methadone, and cocaine to antimorphine, antimethadone, and anticocaine antibodies was measured by SHG, allowing binding affinities and rates of dissociation to be obtained. The SHG primary immunoassay has provided the first kinetic measurements of small-molecule hapten interactions with a receptor antibody. The kinetics reveal for the first time that competitive immunoassays achieve their selectivity by taking advantage of the kinetics of association and dissociation of the labeled and unlabeled target and nontarget small-molecule to the capture antibody. In particular, the induced fit of the target small-molecule to their antibody pairs prolongs their residence time, while the nontarget small-molecule dissociate rapidly in comparison.

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Variability of Plasma Methadone Concentration in Opiate Dependent Receiving Methadone: A Personalised Approach Towards Optimizing Dose

Cited by 2 publications

References 32 publications

The construction and application of a population physiologically based pharmacokinetic model for methadone in Beagles and Greyhounds

The construction and application of a population physiologically based pharmacokinetic model for methadone in Beagles and Greyhounds

Revealing the Kinetic Advantage of a Competitive Small-Molecule Immunoassay by Direct Detection

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