ArticlePharmaceutical research2017
Virtual Clinical Studies to Examine the Probability Distribution of the AUC at Target Tissues Using Physiologically-Based Pharmacokinetic Modeling: Application to Analyses of the Effect of Genetic Polymorphism of Enzymes and Transporters on Irinotecan Induced Side Effects.
Article in Pharmaceutical research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed, 24 citations in OpenAlex.
- Development of an adult whole-body PBPK model of irinotecan and its metabolites for predicting UGT1A1/CYP3A-mediated drug-drug interactions.Frontiers in pharmacology · 2026Article
- Cluster Gauss-Newton method for a quick approximation of profile likelihood: With application to physiologically-based pharmacokinetic models.CPT: pharmacometrics & systems pharmacology · 2024Article
- Physiologically-based pharmacokinetic modeling for investigating the effect of simeprevir on concomitant drugs and an endogenous biomarker of OATP1B.CPT: pharmacometrics & systems pharmacology · 2023Article
- All Roads Lead to Rome: Enhancing the Probability of Target Attainment with Different Pharmacokinetic/Pharmacodynamic Modelling Approaches.Antibiotics (Basel, Switzerland) · 2023Review
- Robust physiologically based pharmacokinetic model of rifampicin for predicting drug-drug interactions via P-glycoprotein induction and inhibition in the intestine, liver, and kidney.CPT: pharmacometrics & systems pharmacology · 2022Article
- Reviewing Data Integrated for PBPK Model Development to Predict Metabolic Drug-Drug Interactions: Shifting Perspectives and Emerging Trends.Frontiers in pharmacology · 2021Review
- Jiawei Xianglian Decoction (JWXLD), a Traditional Chinese Medicine (TCM), Alleviates CPT-11-Induced Diarrhea in Mice.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Utilization of Physiologically Based Pharmacokinetic Modeling in Clinical Pharmacology and Therapeutics: an Overview.Current pharmacology reports · 2020Review
- Physiologically-Based Pharmacokinetic Modeling Analysis for Quantitative Prediction of Renal Transporter-Mediated Interactions Between Metformin and Cimetidine.CPT: pharmacometrics & systems pharmacology · 2019Article
- Application of PBPK Modeling and Virtual Clinical Study Approaches to Predict the Outcomes of CYP2D6 Genotype-Guided Dosing of Tamoxifen.CPT: pharmacometrics & systems pharmacology · 2018Article
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 at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo establish a physiologically-based pharmacokinetic (PBPK) model for analyzing the factors associated with side effects of irinotecan by using a computer-based virtual clinical study (VCS) because many controversial associations between various genetic polymorphisms and side effects of irinotecan have been reported.
methodsTo optimize biochemical parameters of irinotecan and its metabolites in the PBPK modeling, a Cluster Newton method was introduced. In the VCS, virtual patients were generated considering the inter-individual variability and genetic polymorphisms of enzymes and transporters.
resultsApproximately 30 sets of parameters of the PBPK model gave good reproduction of the pharmacokinetics of irinotecan and its metabolites. Of these, 19 sets gave relatively good description of the effect of UGT1A1 *28 and SLCO1B1 c.521T>C polymorphism on the SN-38 plasma concentration, neutropenia, and diarrhea observed in clinical studies reported mainly by Teft et al. (Br J Cancer. 112(5):857-65, 20). VCS also indicated that the frequency of significant association of biliary index with diarrhea was higher than that of UGT1A1 *28 polymorphism.
conclusionThe VCS confirmed the importance of genetic polymorphisms of UGT1A1 *28 and SLCO1B1 c.521T>C in the irinotecan induced side effects. The VCS also indicated that biliary index is a better biomarker of diarrhea than UGT1A1 *28 polymorphism.
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.