ArticleBritish journal of clinical pharmacology2017
Theory-based pharmacokinetics and pharmacodynamics of S- and R-warfarin and effects on international normalized ratio: influence of body size, composition and genotype in cardiac surgery patients.
Article in British journal of clinical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04510805 (Single-blind, Randomized Comparison of Warfarin Management Guided by NextDose Versus Management Based on Clinician Experience.), which is not on this map. Cited by 23 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.
Single-blind, Randomized Comparison of Warfarin Management Guided by NextDose Versus Management Based on Clinician Experience.
Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Population pharmacokinetics and pharmacodynamics of ticagrelor and AR-C124910XX in Chinese healthy male subjects.European journal of clinical pharmacology · 2018Trial
- Model-Based Evaluation of the Warfarin-Sulfamethoxazole Drug-Drug Interaction.European journal of drug metabolism and pharmacokinetics · 2026Article
- AI-assisted warfarin dose optimisation with CURATE.AI for clinical impact: Retrospective data analysis.Bioengineering & translational medicine · 2025Article
- Covariate modeling in pharmacometrics: General points for consideration.CPT: pharmacometrics & systems pharmacology · 2024Review
- A physiologically-based pharmacokinetic/pharmacodynamic modeling approach for drug-drug-gene interaction evaluation of S-warfarin with fluconazole.CPT: pharmacometrics & systems pharmacology · 2024Article
- Dynamics and implications of anti-drug antibodies against adalimumab using ultra-sensitive and highly drug-tolerant assays.Frontiers in immunology · 2024Article
- Deriving mechanism-based pharmacodynamic models by reducing quantitative systems pharmacology models: An application to warfarin.CPT: pharmacometrics & systems pharmacology · 2023Article
- Considerations for Intravenous Anesthesia Dose in Obese Children: Understanding PKPD.Journal of clinical medicine · 2023Review
- A Physiological-Based Pharmacokinetic Model Embedded with a Target-Mediated Drug Disposition Mechanism Can Characterize Single-Dose Warfarin Pharmacokinetic Profiles in Subjects with VariousDrug metabolism and disposition: the biological fate of chemicals · 2023Article
- Delayed concentration effect models for dabigatran anticoagulation.Paediatric anaesthesia · 2022Article
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- TDM is dead. Long live TCI!British journal of clinical pharmacology · 2022Review
- Drug Response Diversity: A Hidden Bacterium?Journal of personalized medicine · 2021Review
- Spotlight Commentary: Model-informed precision dosing must demonstrate improved patient outcomes.British journal of clinical pharmacology · 2019Article
- Warfarin dose requirement in patients having severe thrombosis or thrombophilia.British journal of clinical pharmacology · 2019Article
- Relationship between warfarin dosage and international normalized ratio: a dose-response analysis and evaluation based on multicenter data.European journal of clinical pharmacology · 2019Article
- R-warfarin anticoagulant effect.British journal of clinical pharmacology · 2017Article
- Response to R-warfarin anticoagulant effect.British journal of clinical pharmacology · 2017Article
- Erratum.British journal of clinical pharmacology · 2017Article
Corrections and comments
- Commented on by
- Commented on by
- Erratum issuedErratum.2017
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe aims of this study are to apply a theory-based mechanistic model to describe the pharmacokinetics (PK) and pharmacodynamics (PD) of S- and R-warfarin.
methodsClinical data were obtained from 264 patients. Total concentrations for S- and R-warfarin were measured by ultra-high performance liquid tandem mass spectrometry. Genotypes were measured using pyrosequencing. A sequential population PK parameter with data method was used to describe the international normalized ratio (INR) time course. Data were analyzed with NONMEM. Model evaluation was based on parameter plausibility and prediction-corrected visual predictive checks.
resultsWarfarin PK was described using a one-compartment model. CYP2C9 *1/*3 genotype had reduced clearance for S-warfarin, but increased clearance for R-warfarin. The in vitro parameters for the relationship between prothrombin complex activity (PCA) and INR were markedly different (A = 0.560, B = 0.386) from the theory-based values (A = 1, B = 0). There was a small difference between healthy subjects and patients. A sigmoid E
conclusionA theory-based PKPD model describes warfarin concentrations and clinical response. Expected PK and PD genotype effects were confirmed. The role of predicted fat free mass with theory-based allometric scaling of PK parameters was identified. R-warfarin had a minor effect compared with S-warfarin on PCA synthesis. INR is predictable from 1/PCA in vivo.
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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.