ArticlePharmaceutical research2012
Pharmacokinetic-pharmacodynamic modeling of the D₂ and 5-HT (2A) receptor occupancy of risperidone and paliperidone in rats.
Article in Pharmaceutical research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
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- Differential Effects of Neonatal Ventral Hippocampus Lesion on Behavior and Corticolimbic Plasticity in Wistar-Kyoto and Spontaneously Hypertensive Rats.Neurochemical research · 2024Article
- Pharmacokinetic/pharmacodynamic modeling of cortical dopamine concentrations after quetiapine lipid core nanocapsules administration to schizophrenia phenotyped rats.CPT: pharmacometrics & systems pharmacology · 2024Article
- Risperidone is not only a prodrug: psychosis induced by medication switch from risperidone to paliperidone - a case report.European journal of hospital pharmacy : science and practice · 2023Article
- Dopamine Dynamics and Neurobiology of Non-Response to Antipsychotics, Relevance for Treatment Resistant Schizophrenia: A Systematic Review and Critical Appraisal.Biomedicines · 2023Review
- Enhancing the Antipsychotic Effect of Risperidone by Increasing Its Binding Affinity to Serotonin Receptor via Picric Acid: A Molecular Dynamics Simulation.Pharmaceuticals (Basel, Switzerland) · 2022Article
- The Kinetic Component in Drug Discovery: Using the Most Basic Pharmacological Concepts to Advance in Selecting Drugs to Combat CNS Diseases.Current neuropharmacology · 2020Review
- CDI cross-linked β-cyclodextrin nanosponges of paliperidone: synthesis and physicochemical characterization.Journal of materials science. Materials in medicine · 2019Article
- Impact of mathematical pharmacology on practice and theory: four case studies.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- Article
- Understanding the Behavior of Systems Pharmacology Models Using Mathematical Analysis of Differential Equations: Prolactin Modeling as a Case Study.CPT: pharmacometrics & systems pharmacology · 2016Article
- Translational Modeling in Schizophrenia: Predicting Human Dopamine D2 Receptor Occupancy.Pharmaceutical research · 2016Article
- Pharmacogenomic Study Reveals New Variants of Drug Metabolizing Enzyme and Transporter Genes Associated with Steady-State Plasma Concentrations of Risperidone and 9-Hydroxyrisperidone in Thai Autism Spectrum Disorder Patients.Frontiers in pharmacology · 2016Article
- No change of the lipid profile under the control of ApoE gene polymorphism in schizophrenics under paliperidone treatment.The Psychiatric quarterly · 2014Article
- Dopamine D2 receptor occupancy as a predictor of catalepsy in rats: a pharmacokinetic-pharmacodynamic modeling approach.Pharmaceutical research · 2014Article
- Prediction of brain clozapine and norclozapine concentrations in humans from a scaled pharmacokinetic model for rat brain and plasma pharmacokinetics.Journal of translational medicine · 2014Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeA pharmacokinetic-pharmacodynamic (PK-PD) model was developed to describe the time course of brain concentration and dopamine D₂ and serotonin 5-HT(2A) receptor occupancy (RO) of the atypical antipsychotic drugs risperidone and paliperidone in rats.
methodsA population approach was utilized to describe the PK-PD of risperidone and paliperidone using plasma and brain concentrations and D₂ and 5-HT(2A) RO data. A previously published physiology- and mechanism-based (PBPKPD) model describing brain concentrations and D₂ receptor binding in the striatum was expanded to include metabolite kinetics, active efflux from brain, and binding to 5-HT(2A) receptors in the frontal cortex.
resultsA two-compartment model best fit to the plasma PK profile of risperidone and paliperidone. The expanded PBPKPD model described brain concentrations and D₂ and 5-HT(2A) RO well. Inclusion of binding to 5-HT(2A) receptors was necessary to describe observed brain-to-plasma ratios accurately. Simulations showed that receptor affinity strongly influences brain-to-plasma ratio pattern.
conclusionBinding to both D₂ and 5-HT(2A) receptors influences brain distribution of risperidone and paliperidone. This may stem from their high affinity for D₂ and 5-HT(2A) receptors. Receptor affinities and brain-to-plasma ratios may need to be considered before choosing the best PK-PD model for centrally active drugs.
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