Trial reportBritish journal of clinical pharmacology2016
Population pharmacokinetic/pharmacodynamic modelling of the effects of axomadol and its O-demethyl metabolite on pupil diameter and nociception in healthy subjects.
Trial report in British journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.
- Oxycodone Effect on Pupil Constriction in Recreational Opioid Users: A Pharmacokinetic/Pharmacodynamic Meta-Analysis Approach.Clinical pharmacokinetics · 2021Pooled it
- Population pharmacokinetic/pharmacodynamic modelling of the effects of axomadol and its O-demethyl metabolite on pupil diameter and nociception in healthy subjects.British journal of clinical pharmacology · 2016Trial
- Population Pharmacokinetic-Pharmacodynamic Analysis of a Reserpine-Induced Myalgia Model in Rats.Pharmaceutics · 2024Article
- Semimechanistic models to relate noxious stimulation, movement, and pupillary dilation responses in the presence of opioids.CPT: pharmacometrics & systems pharmacology · 2022Article
- The effects of aripiprazole and olanzapine on pupillary light reflex and its relationship with pharmacogenetics in a randomized multiple-dose trial.British journal of clinical pharmacology · 2020Article
- Assessment of the Inter-Batch Variability of Microstructure Parameters in Topical Semisolids and Impact on the Demonstration of Equivalence.Pharmaceutics · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe aim of the present study was to characterize the pharmacokinetic/pharmacodynamic (PK/PD) properties of the active components of axomadol and to quantify their contribution to observed the pupillometric and analgesic (measured through the cold pressor test) effects linking the PD engagement biomarker with clinical response.
methodsHealthy subjects (n = 74) received either placebo or axomadol orally at doses ranging from 66 mg to 225 mg following multiple dosing regimens in two separate clinical trials. Plasma concentrations of the two enantiomers of axomadol and their metabolites, and PD responses were measured at specific times. The population analysis was performed using NONMEM 7.2.
resultsThe kinetics of the parent drug and its metabolite could be described simultaneously using an extra compartment mimicking the liver, where the metabolite is formed. The SS parent compound elicited a plasma concentration-dependent increase in pupil diameter, with estimates (percentage relative standard errors) of maximal effect (Emax ) and plasma concentration exerting a half-maximal effect (C50 ) of 0.79 (17.4) mm, and 90.7 (27) ng ml(-1) , respectively. The predicted effect site concentrations of the RR O-demethyl metabolite decreased the pupil diameter linearly, with an estimate of the slope of 0.00967 (18.7) mm·ml ng(-1) . An additive model, integrating the net effect on pupil diameter, described adequately the reduction in pain with a linear function. The PK/PD model revealed that each 0.5 mm change in pupil diameter is associated with a 10% decrease in cold pressor area under the concentration-time curve effects.
conclusionsThe PK/PD analysis performed enabled the individual contributions of the active compounds to the observed effects to be identified and quantified. These effects were in accordance with the known mechanisms of action - namely, opioid agonism and noradrenaline reuptake inhibition.
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Registered trials
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