ArticlePharmaceutical research2008
Semi-mechanistic pharmacokinetic/pharmacodynamic modelling of the antinociceptive response in the presence of competitive antagonism: the interaction between tramadol and its active metabolite on micro-opioid agonism and monoamine reuptake inhibition, in the rat.
Article in Pharmaceutical research, 2008. 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.
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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.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- A Systematic Review of Laboratory Evidence for the Abuse Potential of Tramadol in Humans.Frontiers in psychiatry · 2019Pooled 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
- The impact of composite AUC estimates on the prediction of systemic exposure in toxicology experiments.Journal of pharmacokinetics and pharmacodynamics · 2015Article
- The mu-opioid receptor agonist/noradrenaline reuptake inhibition (MOR-NRI) concept in analgesia: the case of tapentadol.CNS drugs · 2014Review
- Translational PK-PD modeling in pain.Journal of pharmacokinetics and pharmacodynamics · 2013Review
- Semi-mechanistic modeling of the interaction between the central and peripheral effects in the antinociceptive response to lumiracoxib in rats.The AAPS journal · 2012Article
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 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo establish a semi-mechanistic pharmacokinetic/pharmacodynamic (pk/pd) model for racemic tramadol (T) integrating all the components with a significant contribution to T effects in rats, using cold allodynia in the Bennett model of neuropathic pain.
methodsMale Sprague-Dawley rats (n=53) were randomly allocated in six groups receiving saline, racemic T (5 mg/kg), RR-T (5 mg/kg), SS-T (5 mg/kg), RR-O-demethyltramadol [RR-M1 (1 mg/kg)] or SS-M1 (30 mg/kg) in two h intravenous infusion.
resultsThe mu-opioid effects of RR-M1 (E(RR-M1)) were described with an effect compartment model. Contribution to analgesic response of RR-T resulted negligible. The monoamine re-uptake inhibition effects (ESS-M1,T) were modelled as an indirect response model incorporating a competitive interaction between SS-T and SS-M1. ERR-M1 and ESS-M1,T were finally considered as a two independent stimuli converging into a single and common antinoceptive stimulus. The estimates of the steady-state plasma concentrations eliciting half of maximum response for RR-M1, SS-T, and SS-M1 were 20.2, 230, and 869 ng/ml, respectively. RR-M1 is the main active component, but SS-T having a significant contribution.
conclusionCold allodynia in the Bennett model has proven an adequate experimental set up to develop complex pk/pd models in analgesia involving different mechanisms of action.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.