ArticleClinical pharmacokinetics2025
Population Pharmacokinetics Model of Thioguanine in Patients with Inflammatory Bowel Disease.
Article in Clinical pharmacokinetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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
1 citing paper in PubMed.
- Drug-Drug Interactions and Individualized Clozapine Therapy in Patients with Depression: Insights from Real-World Data.Drug design, development and therapy · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThioguanine (TG) has recently been rediscovered as an immunosuppressive agent in the treatment of inflammatory bowel disease (IBD). This prodrug is directly converted into its active metabolites, 6-thioguanine nucleotides (6-TGNs), targeting the inhibition of RAC1 GTPase in inflammatory conditions, disrupting key cellular signaling pathways necessary for T-cell activation and survival, thereby contributing to its immunosuppressive action. In IBD, TG is used fixed dose and may benefit from model-informed precision dosing (MIPD) to optimize treatment efficacy and minimize toxicity. However, a population pharmacokinetic (PopPK) model to do so is lacking.
objectiveTo develop a PopPK model for TG in IBD patients, enhancing the understanding of TG's pharmacokinetics and supporting the implementation of model-informed precision dosing (MIPD).
methodsWe employed a dataset comprising 131 6-TGN trough concentrations from 28 IBD patients treated with TG. The data were analyzed using nonlinear mixed-effects modeling (NONMEM) to estimate pharmacokinetic parameters and explore the influence of covariates such as weight and 5-ASA use on drug disposition. Model fit-for-purpose was evaluated through computation of the model's forecasting performance.
resultsThe developed PopPK model was a one-compartment model with first-order absorption. A one-compartment TG model was stable, and able to estimate pharmacokinetic parameters with good precision (relative standard error [RSE] 15%) with weight and aminosalicylic acid (5-ASA) use significantly affected TG clearance. Forecasting performance was also adequate with a relative root mean squared error (rRMSE) of 24.1% and practically no systematic bias (mean percentage error [MPE] 0.2%).
conclusionThis study presents the first PopPK model of thioguanine for IBD, offering a novel tool for MIPD in clinical settings. Future studies should explore additional covariates such as TPMT genotype and drug interactions to further refine dosing recommendations for diverse patient populations.
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.