Trial reportBritish journal of clinical pharmacology2003
Physiologically based modelling of inhibition of metabolism and assessment of the relative potency of drug and metabolite: dextromethorphan vs. dextrorphan using quinidine inhibition.
Trial report in British journal of clinical pharmacology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
14 citing papers in PubMed, 43 citations in OpenAlex.
- Dextromethorphan Versus Dextrorphan: A Quantitative Comparison of Antitussive Potency Following Separate Administration of Metabolite.Journal of clinical pharmacology · 2025Trial
- Population pharmacokinetic analysis for nelfinavir and its metabolite M8 in virologically controlled HIV-infected patients on HAART.British journal of clinical pharmacology · 2005Trial
- The effect of quinidine, used as a probe for the involvement of P-glycoprotein, on the intestinal absorption and pharmacodynamics of methadone.British journal of clinical pharmacology · 2004Trial
- A clinical pharmacokinetic drug-drug interaction study between dextromethorphan and emvododstat, a potent anti-SARS-CoV-2 dihydroorotate dehydrogenase inhibitor.European journal of clinical pharmacology · 2023Article
- Physiologically-based pharmacokinetic modeling of quinidine to establish a CYP3A4, P-gp, and CYP2D6 drug-drug-gene interaction network.CPT: pharmacometrics & systems pharmacology · 2023Article
- Physiologically based pharmacokinetic (PBPK) modeling of the role of CYP2D6 polymorphism for metabolic phenotyping with dextromethorphan.Frontiers in pharmacology · 2022Article
- How to Choose In Vitro Systems to Predict In Vivo Drug Clearance: A System Pharmacology Perspective.BioMed research international · 2015Article
- Population pharmacokinetic modelling to assess the impact of CYP2D6 and CYP3A metabolic phenotypes on the pharmacokinetics of tamoxifen and endoxifen.British journal of clinical pharmacology · 2014Article
- Pharmacokinetic profile of dextromethorphan hydrobromide in a syrup formulation in children and adolescents.Clinical drug investigation · 2014Article
- A physiologically based pharmacokinetic model to predict disposition of CYP2D6 and CYP1A2 metabolized drugs in pregnant women.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- The design and analysis of parallel experiments to produce structurally identifiable models.Journal of pharmacokinetics and pharmacodynamics · 2013Article
- Dextromethorphan/quinidine: in pseudobulbar affect.CNS drugs · 2011Review
- Contribution of the active metabolite M1 to the pharmacological activity of tesofensine in vivo: a pharmacokinetic-pharmacodynamic modelling approach.British journal of pharmacology · 2008Article
- Physiologically based pharmacokinetic modelling: a sound mechanistic basis is needed.British journal of clinical pharmacology · 2005Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo define the relative antitussive effect of dextromethorphan (DEX) and its primary metabolite dextrorphan (DOR) after administration of DEX.
methodsData were analysed from a double-blind, randomized cross-over study in which 22 subjects received the following oral treatments: (i) placebo; (ii) 30 mg DEX hydro-bromide; (iii) 60 mg DEX hydro-bromide; and (iv) 30 mg DEX hydro-bromide preceded at 1 h by quinidine HCl (50 mg). Cough was elicited using citric acid challenge. Pharmacokinetic data from all non-placebo arms of the study were fitted simultaneously. The parameters were then used as covariates in a link PK-PD model of cough suppression using data from all treatment arms.
resultsThe best-fit PK model assumed two- and one-compartment PK models for DEX and DOR, respectively, and competitive inhibition of DEX metabolism by quinidine. The intrinsic clearance of DEX estimated from the model ranged from 59 to 1536 l x h(-1), which overlapped with that extrapolated from in vitro data (12-261 l x h(-1)) and showed similar variation (26- vs. 21-fold, respectively). The inhibitory effect of quinidine ([I]/Ki) was 19 (95% confidence interval of mean: 18-20) with an estimated average Ki of 0.017 microM. Although DEX and DOR were both active, the potency of the antitussive effect of DOR was 38% that of DEX. A sustained antitussive effect was related to slow removal of DEX/DOR from the effect site (ke0 = 0.07 h(-1)).
conclusionsPhysiologically based PK modelling with perturbation of metabolism using an inhibitor allowed evaluation of the antitussive potency of DOR without the need for separate administration of DOR.
Indexed as
Identifiers
What OpenQuestion holds
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.