Trial reportClinical pharmacokinetics2013
Physiologically based pharmacokinetic modelling to predict single- and multiple-dose human pharmacokinetics of bitopertin.
Trial report in Clinical pharmacokinetics, 2013. 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
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, 16 citations in OpenAlex.
- Effects of Cytochrome P450 3A4 Inhibitors-Ketoconazole and Erythromycin-on Bitopertin Pharmacokinetics and Comparison with Physiologically Based Modelling Predictions.Clinical pharmacokinetics · 2016Trial
- In Silico Post-screening of Anti-polymerization Agents to Treat Sickle Cell Disease.bioRxiv : the preprint server for biology · 2025Article
- Phase I clinical trial of NH130 and the prediction of its pharmacokinetics using physiologically based pharmacokinetic modeling.Frontiers in pharmacology · 2024Article
- Pharmacokinetic profile of bitopertin, a selective GlyTNaunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Introduction of an artificial neural network-based method for concentration-time predictions.CPT: pharmacometrics & systems pharmacology · 2022Article
- First-in-human study to investigate the safety and pharmacokinetics of salvianolic acid A and pharmacokinetic simulation using a physiologically based pharmacokinetic model.Frontiers in pharmacology · 2022Article
- Progress in Prediction and Interpretation of Clinically Relevant Metabolic Drug-Drug Interactions: a Minireview Illustrating Recent Developments and Current Opportunities.Current pharmacology reports · 2017Review
- Effects of the glycine reuptake inhibitors bitopertin and RG7118 on glycine in cerebrospinal fluid: results of two proofs of mechanism studies in healthy volunteers.Psychopharmacology · 2016Article
- Combining 'Bottom-Up' and 'Top-Down' Methods to Assess Ethnic Difference in Clearance: Bitopertin as an Example.Clinical pharmacokinetics · 2016Article
- Physiologically based absorption modelling to predict the impact of drug properties on pharmacokinetics of bitopertin.The AAPS journal · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBitopertin (RG1678) is a glycine reuptake inhibitor currently in phase 3 trials for treatment of schizophrenia. This paper describes the use of physiologically based pharmacokinetic (PBPK) modelling and preclinical data to gain insights into and predict bitopertin clinical pharmacokinetics.
methodsSimulations of pharmacokinetics were initiated early in the drug discovery stage by integrating physicochemical properties and in vitro measurements into a PBPK rat model. Comparison of pharmacokinetics predicted by PBPK modelling with those measured after intravenous and oral dosing in rats and monkeys showed a good match and thus increased confidence that a similar approach could be applied for human prediction. After comparison of predicted plasma concentrations with those measured after single oral doses in the first clinical study, the human model was refined and then applied to simulate multiple-dose pharmacokinetics.
resultsClinical plasma concentrations measured were in good agreement with PBPK predictions. Predicted area under the plasma concentration-time curve (AUC) was within twofold of the observed mean values for all dose levels. Maximum plasma concentration (C max) at higher doses was well predicted but approximately twofold below observed values at the lower doses. A slightly less than dose-proportional increase in both AUC and C max was observed, and model simulations indicated that when the dose exceeded 50 mg, solubility limited the fraction of dose absorbed. Refinement of the absorption model with additional solubility and permeability measurements further improved the match of simulations to observed single-dose data. Simulated multiple-dose pharmacokinetics with the refined model were in good agreement with observed data.
conclusionsClinical pharmacokinetics of bitopertin can be well simulated with a mechanistic PBPK model. This model supports further clinical development and provides a valuable repository for pharmacokinetic knowledge gained about the molecule.
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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.