Trial reportEuropean journal of clinical pharmacology2007
Pharmacokinetic-pharmacodynamic modeling of the miotic effects of dihydrocodeine in humans.
Trial report in European journal of clinical pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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
3 citing papers in PubMed, 6 citations in OpenAlex.
- Semimechanistic models to relate noxious stimulation, movement, and pupillary dilation responses in the presence of opioids.CPT: pharmacometrics & systems pharmacology · 2022Article
- UPLC-MS-MS Determination of Dihydrocodeine in Human Plasma and Its Application to a Pharmacokinetic Study.Journal of chromatographic science · 2016Article
- Pupillary responses to intranasal trigeminal and olfactory stimulation.Journal of neural transmission (Vienna, Austria : 1996) · 2009Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe purpose of this study was to evaluate the pharmacokinetic-pharmacodynamic interrelations of pupillary effects of dihydrocodeine by two different analytic approaches.
methodsDihydrocodeine plasma concentrations and miotic effects were available from a previous study with 24-h measurements after administration of 60 mg dihydrocodeine to nine healthy young men. Plasma concentration versus time course was described either by a one-compartment model or by linear splines using NONMEM. Dihydrocodeine concentrations at the effect site were obtained by convolution of a first-order transfer function with the function describing the plasma concentration versus time courses, and miotic effects were related to effect-site concentrations by a sigmoidal pharmacodynamic model.
resultsBayesian individual fits of miotic effects were only slightly better with the spline approach than with the compartmental approach (median individual absolute weighted residuals 0.046 versus 0.058, respectively, Wilcoxon test p = 0.008; residual errors of an additive error model 0.0979 versus 0.184, respectively). Both approaches provided similar pharmacokinetic-pharmacodynamic population parameter values. The transfer half-life between plasma and effect site was 21.1 min (95% CI 11.1-34.7 min) and 19.8 min (95% CI 11.9-34 min) with spline and compartmental approaches, respectively, and miosis occurred with EC50 of 207 or 230 ng/ml, respectively.
conclusionTwo modeling approaches to the miotic effects of dihydrocodeine provided similar transfer half-lives between plasma and effect site, which also agreed with previous independently estimated values obtained from analgesic effects, suggesting that pupil size is a valid biomarker to estimate the value of ke0 for opioid central nervous system (CNS) effects.
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Registered trials
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