ArticleInvestigational new drugs2010
Scaling the time-course of myelosuppression from rats to patients with a semi-physiological model.
Article in Investigational new drugs, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Structural identifiability for mathematical pharmacology: models of myelosuppression.Journal of pharmacokinetics and pharmacodynamics · 2018Pooled it
- Model-based assessment of neutrophil-mediated phagocytosis and digestion of bacteria across in vitro and in vivo studies.CPT: pharmacometrics & systems pharmacology · 2023Article
- A comprehensive regulatory and industry review of modeling and simulation practices in oncology clinical drug development.Journal of pharmacokinetics and pharmacodynamics · 2023Review
- The evolving role of investigative toxicology in the pharmaceutical industry.Nature reviews. Drug discovery · 2023Review
- Free Drug Theory - No Longer Just a Hypothesis?Pharmaceutical research · 2022Article
- Translational approach from preclinical to clinical: comparison of dose finding methods of a new Bcl2 inhibitor using PK-PD modeling and interspecies extrapolation.Investigational new drugs · 2020Article
- Steering the Clinical Translation of Delivery Systems for Drugs and Health Products.Pharmaceutics · 2020Article
- Quantifying Drug-Induced Bone Marrow Toxicity Using a Novel Haematopoiesis Systems Pharmacology Model.CPT: pharmacometrics & systems pharmacology · 2019Article
- A Data Mining-Based Analysis of Medication Rules in Treating Bone Marrow Suppression by Kidney-Tonifying Method.Evidence-based complementary and alternative medicine : eCAM · 2019Review
- Quantitative translational modeling to facilitate preclinical to clinical efficacy & toxicity translation in oncology.Future science OA · 2018Review
- Pharmacokinetic-pharmacodynamic modelling of neutrophil response to G-CSF in healthy subjects and patients with chemotherapy-induced neutropenia.British journal of clinical pharmacology · 2018Article
- Model-Based Adaptive Optimal Design (MBAOD) Improves Combination Dose Finding Designs: an Example in Oncology.The AAPS journal · 2018Article
- Systems Pharmacology Model of Gastrointestinal Damage Predicts Species Differences and Optimizes Clinical Dosing Schedules.CPT: pharmacometrics & systems pharmacology · 2018Article
- Generation of Methicillin-Resistant Staphylococcus Aureus Biofilm Infection in an Immunosuppressed Rat Model.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Translational Modeling of Drug-Induced Myelosuppression and Effect of Pretreatment Myelosuppression for AZD5153, a Selective BRD4 Inhibitor.CPT: pharmacometrics & systems pharmacology · 2017Article
- Designing More Efficient Preclinical Experiments: A Simulation Study in Chemotherapy-Induced Myelosupression.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- Modeling and Simulation Approaches for Cardiovascular Function and Their Role in Safety Assessment.CPT: pharmacometrics & systems pharmacology · 2015Review
- Article
- Population pharmacokinetic-pharmacodynamic analysis for eribulin mesilate-associated neutropenia.British journal of clinical pharmacology · 2013Article
- Predictions of in vivo prolactin levels from in vitro K(i) values of D(2) receptor antagonists using an agonist-antagonist interaction model.The AAPS journal · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo investigate the potential of a model for chemotherapy-induced myelosuppression to predict the full time-course of myelosuppression in patients based on rat data.
methodsWhite blood cell counts were determined in rats after administration of 5-fluorouracil, epirubicin, cyclophosphamide, docetaxel, paclitaxel or etoposide. Pharmacokinetic models were used to predict the concentration-time profile in each rat. A semi-physiological model of myelosuppression was applied to the rat data. The drug-related parameter Slope was allowed to differ between drugs. The analysis was performed in NONMEM VI. Time-courses of myelosuppression in patients were predicted for each drug based on patient pharmacokinetic models, typical system-related parameters previously determined in patients and the rat Slope estimates in the present study.
resultsThe semi-physiological model of myelosuppression fit the rat data well and the estimated maturation time in rats (53 h) was approximately half of the previous estimate in patients. The relative difference in Slope estimates for rats and patients based on total drug concentrations ranged between 28% to 8-fold for the six drugs. The differences reduced to 8-37% for all drugs when correcting the rat Slope estimates for species difference in protein binding and in CFU-GM assay sensitivity.
conclusionsThis method for interspecies scaling was successful in predicting the time-course of myelosuppression in patients based on rat data. Predictions improved when species differences in protein binding and CFU-GM assay sensitivity were accounted for. The approach appears promising for predicting myelosuppression in patients early in development.
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.