Evidence map›Paper›PMID 41774388›Full record

ArticleEuropean journal of drug metabolism and pharmacokinetics2026

Role of Pharmacogenetics on Tramadol Pharmacokinetics: A Population Pharmacokinetic Model.

Paula Soria-Chacartegui, Gudrun Würthwein, Pablo Zubiaur, Susana Almenara, Dolores Ochoa, Francisco Abad-Santos, Georg Hempel

Abstract read
In one paragraph

Article in European journal of drug metabolism and pharmacokinetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from 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.

2 · The registry

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

7 authors.

Paula Soria-ChacarteguiClinical Pharmacology Department, Hospital Universitario de La Princesa, Pharmacology Department, Faculty of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria la Princesa (IIS-Princesa), Madrid, Spain.ORCID http://orcid.org/0000-0002-1951-2626
Gudrun WürthweinWestfälische Wilhelms-Universität Münster, Institut für Pharmazeutische und Medizinische Chemie-Klinische Pharmazie, Corrensstraße 48, 48149, Münster, Germany.ORCID http://orcid.org/0000-0002-7617-183X
Pablo ZubiaurClinical Pharmacology Department, Hospital Universitario de La Princesa, Pharmacology Department, Faculty of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria la Princesa (IIS-Princesa), Madrid, Spain.ORCID http://orcid.org/0000-0002-6150-4320
Susana AlmenaraClinical Pharmacology Department, Hospital Universitario de La Princesa, Pharmacology Department, Faculty of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria la Princesa (IIS-Princesa), Madrid, Spain.ORCID http://orcid.org/0000-0003-2619-191X
Dolores OchoaClinical Pharmacology Department, Hospital Universitario de La Princesa, Pharmacology Department, Faculty of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria la Princesa (IIS-Princesa), Madrid, Spain.ORCID http://orcid.org/0000-0002-1265-6600
Francisco Abad-SantosClinical Pharmacology Department, Hospital Universitario de La Princesa, Pharmacology Department, Faculty of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria la Princesa (IIS-Princesa), Madrid, Spain.ORCID http://orcid.org/0000-0002-6519-8885
Georg HempelWestfälische Wilhelms-Universität Münster, Institut für Pharmazeutische und Medizinische Chemie-Klinische Pharmazie, Corrensstraße 48, 48149, Münster, Germany. hempege@uni-muenster.de.ORCID http://orcid.org/0000-0002-5790-6423

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveTramadol is a widely used opioid, and pharmacogenetics is partially responsible for the variability in its response. The objective was to develop a tramadol population pharmacokinetic (popPK) model including pharmacogenetic information.

methodsA single oral dose of 37.5 mg tramadol + 400 mg ibuprofen arginine was administered to 24 European healthy volunteers, and 18 blood samples were obtained from 0.25 h to 24 h after drug intake. Subjects were genotyped for the main pharmacogenes and a popPK model was built using NONMEM

resultsA two-compartment model, with transit absorption into the depot compartment and first-order elimination, was the best fit to the data. In total, 8 volunteers were CYP2D6 intermediate metabolizers (IMs) and 14 were normal metabolizers (NMs), merged for the analysis with the two ultrarapid metabolizers (UMs), whereas no poor metabolizers (PMs) were present (European frequencies: 38.3%, 49.2%, 2.3%, and 6.5%, respectively). CYP2D6 phenotype affected clearance, which was 20% reduced in IMs compared with NMs + UMs. CYP2B6 (NMs = 11, IMs = 11, and PMs = 2) and CYP3A4 (NMs = 20, IMs = 3) phenotypes did not affect clearance. PopPK and NCA estimates were in close agreement. Simulations indicated a 20% and even 40% higher area under the curve after single dose and steady state conditions, respectively, in CYP2D6 IMs compared with NMs and UMs.

conclusionsA popPK model including CYP2D6 phenotype well described the data. Further research with increased sample size is needed to analyze the clinical impact and effect of CYP2B6 and CYP3A4 phenotype on tramadol pharmacokinetics.

Indexed as

Analgesics, OpioidModels, BiologicalTramadolAdministration, OralAdultCytochrome P-450 CYP2B6Cytochrome P-450 CYP2D6Cytochrome P-450 CYP3AFemaleGenotypeHumansMalePharmacogeneticsPhenotypeYoung AdultAnalgesics, OpioidCYP2B6 protein, humanCYP3A4 protein, humanCytochrome P-450 CYP2B6Cytochrome P-450 CYP2D6Cytochrome P-450 CYP3ATramadol

Identifiers

PMID41774388
PMCPMC13031194

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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.