ArticlePharmaceutical research2008
Pharmacokinetic modeling of non-linear brain distribution of fluvoxamine in the rat.
Article in Pharmaceutical research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
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- In Vitro to In Vivo Extrapolation Linked to Physiologically Based Pharmacokinetic Models for Assessing the Brain Drug Disposition.The AAPS journal · 2022Review
- Pharmacokinetic Modeling of the Impact of P-glycoprotein on Ondansetron Disposition in the Central Nervous System.Pharmaceutical research · 2020Article
- Development of a Physiologically Based Pharmacokinetic/Pharmacodynamic Model to Predict the Impact of Genetic Polymorphisms on the Pharmacokinetics and Pharmacodynamics Represented by Receptor/Transporter Occupancy of Central Nervous System Drugs.Clinical pharmacokinetics · 2016Article
- Physiologically based pharmacokinetic modelling of drug penetration across the blood-brain barrier--towards a mechanistic IVIVE-based approach.The AAPS journal · 2013Review
- Modeling bioavailability to organs protected by biological barriers.In silico pharmacology · 2013Review
- Atazanavir-bilirubin interaction: a pharmacokinetic-pharmacodynamic model.Clinical pharmacology : advances and applications · 2013Article
- Impact of efflux transporters and of seizures on the pharmacokinetics of oxcarbazepine metabolite in the rat brain.British journal of pharmacology · 2008Article
- Pharmacokinetic-pharmacodynamic modelling of fluvoxamine 5-HT transporter occupancy in rat frontal cortex.British journal of pharmacology · 2008Article
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Authors and funding
4 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionA pharmacokinetic (PK) model is proposed for estimation of total and free brain concentrations of fluvoxamine. MATERIALS AND
methodsRats with arterial and venous cannulas and a microdialysis probe in the frontal cortex received intravenous infusions of 1, 3.7 or 7.3 mg.kg(-1) of fluvoxamine. ANALYSIS: With increasing dose a disproportional increase in brain concentrations was observed. The kinetics of brain distribution was estimated by simultaneous analysis of plasma, free brain ECF and total brain tissue concentrations. The PK model consists of three compartments for fluvoxamine concentrations in plasma in combination with a catenary two compartment model for distribution into the brain. In this catenary model, the mass exchange between a shallow perfusion-limited and a deep brain compartment is described by a passive diffusion term and a saturable active efflux term.
resultsThe model resulted in precise estimates of the parameters describing passive influx into (k in) of 0.16 min(-1) and efflux from the shallow brain compartment (k out) of 0.019 min(-1) and the fluvoxamine concentration at which 50% of the maximum active efflux (C 50) is reached of 710 ng.ml(-1). The proposed brain distribution model constitutes a basis for precise characterization of the PK-PD correlation of fluvoxamine by taking into account the non-linearity in brain distribution.
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