ArticleCPT: pharmacometrics & systems pharmacology2012
Pharmacokinetic-pharmacodynamic modeling of severity levels of extrapyramidal side effects with markov elements.
Article in CPT: pharmacometrics & systems pharmacology, 2012. 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
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The trial behind it
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Who cites it
10 citing papers in PubMed, 26 citations in OpenAlex.
- A Modeling and Simulation Framework for Adverse Events in Erlotinib-Treated Non-Small-Cell Lung Cancer Patients.The AAPS journal · 2015Trial
- Exposure-response modeling for nausea incidence for cotadutide using a Markov modeling approach.CPT: pharmacometrics & systems pharmacology · 2024Article
- Rituximab pharmacokinetic and pharmacokinetic-pharmacodynamic evaluation based on a study in diffuse large B-cell lymphoma: Influence of tumor size on pharmacokinetic and assessment of pharmacokinetic similarity.CPT: pharmacometrics & systems pharmacology · 2023Article
- Analysis of Longitudinal-Ordered Categorical Data for Muscle Spasm Adverse Event of Vismodegib: Comparison Between Different Pharmacometric Models.CPT: pharmacometrics & systems pharmacology · 2020Article
- A Minimal Continuous-Time Markov Pharmacometric Model.The AAPS journal · 2017Article
- Simultaneous Exposure-Response Modeling of ACR20, ACR50, and ACR70 Improvement Scores in Rheumatoid Arthritis Patients Treated With Certolizumab Pegol.CPT: pharmacometrics & systems pharmacology · 2014Article
- Dopamine D2 receptor occupancy as a predictor of catalepsy in rats: a pharmacokinetic-pharmacodynamic modeling approach.Pharmaceutical research · 2014Article
- Optimal sampling of antipsychotic medicines: a pharmacometric approach for clinical practice.British journal of clinical pharmacology · 2014Article
- Modelling and simulation of placebo effect: application to drug development in schizophrenia.Journal of pharmacokinetics and pharmacodynamics · 2013Review
- CPT: Pharmacometrics and Systems Pharmacology.CPT: pharmacometrics & systems pharmacology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A major problem in the treatment of schizophrenic patients with current antipsychotic drugs, mainly acting as dopamine-2 receptor antagonists, is the occurrence of side effects such as extrapyramidal symptoms (EPS). Meta-analyses of summary data of EPS occurrence, and receptor occupancies inferred from mean plasma concentrations, have shown the incidence of EPS to rise when receptor occupancy is above ~80%. In this analysis, individual longitudinal EPS data from 2,630 patients participating in one of seven different trials and treated with haloperidol, paliperidone, ziprasidone, olanzapine, JNJ-37822681, or placebo were analyzed using a continuous time probability model with Markov elements. The developed pharmacokinetic-pharmacodynamic model describes the longitudinal changes of spontaneously reported EPS-related adverse events and their severity levels rated by clinicians. Individual steady-state concentrations and occupancy levels were found to be predictors for EPS. The results confirm 80% occupancy as a level of increased EPS occurrence rates, also at the individual level.CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e1; doi:10.1038/psp.2012.9; advance online publication 26 September 2012.
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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.