ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2011
Prediction of repeat-dose occupancy from single-dose data: characterisation of the relationship between plasma pharmacokinetics and brain target occupancy.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The relationship between dose and serotonin transporter occupancy of antidepressants-a systematic review.Molecular psychiatry · 2022Pooled it
- Predicting brain occupancy from plasma levels using PET: superiority of combining pharmacokinetics with pharmacodynamics while modeling the relationship.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2012Trial
- Pharmacological differentiation of opioid receptor antagonists by molecular and functional imaging of target occupancy and food reward-related brain activation in humans.Molecular psychiatry · 2011Trial
- An Open-Label Study Investigating the 5-HTClinical pharmacology in drug development · 2026Article
- Estimation of target occupancy in repeated dosing design studies using positron emission tomography: Biases due to target upregulation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Therapeutic reference range for duloxetine in the treatment of depression revised: A systematic review and meta-analysis.Neuroscience applied · 2024Review
- Drug characteristics derived from kinetic modeling: combinedEJNMMI research · 2022Article
- In Vivo Studies of Drug BBB Transport: Translational Challenges and the Role of Brain Imaging.Handbook of experimental pharmacology · 2022Article
- Mechanistic Multilayer Quantitative Model for Nonlinear Pharmacokinetics, Target Occupancy and Pharmacodynamics (PK/TO/PD) Relationship of D-Amino Acid Oxidase Inhibitor, TAK-831 in Mice.Pharmaceutical research · 2020Article
- Analysis of PK11195 concentrations in rodent whole blood and tissue samples by rapid and reproducible chromatographic method to support target-occupancy PET studies.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2019Article
- Occupancy of Norepinephrine Transporter by Duloxetine in Human Brains Measured by Positron Emission Tomography with (S,S)-[18F]FMeNER-D2.The international journal of neuropsychopharmacology · 2017Article
- Receptor Occupancy of the κ-Opioid Antagonist LY2456302 Measured with Positron Emission Tomography and the Novel Radiotracer 11C-LY2795050.The Journal of pharmacology and experimental therapeutics · 2016Article
- Preclinical to clinical translation of CNS transporter occupancy of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.The international journal of neuropsychopharmacology · 2014Article
- An evaluation of the brain distribution of [(11)C]GSK1034702, a muscarinic-1 (M 1) positive allosteric modulator in the living human brain using positron emission tomography.EJNMMI research · 2014Article
- Article
- Determination of dopamine D₂ receptor occupancy by lurasidone using positron emission tomography in healthy male subjects.Psychopharmacology · 2013Article
- Kinetic analysis of drug-target interactions with PET for characterization of pharmacological hysteresis.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2013Article
- Article
- D₂-receptor occupancy measurement of JNJ-37822681, a novel fast off-rate D₂-receptor antagonist, in healthy subjects using positron emission tomography: single dose versus steady state and dose selection.Psychopharmacology · 2012Article
- Pharmacokinetic modeling of P-glycoprotein function at the rat and human blood-brain barriers studied with (R)-[11C]verapamil positron emission tomography.EJNMMI research · 2012Article
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Positron emission tomography (PET) is used in drug development to assist dose selection and to establish the relationship between blood and tissue pharmacokinetics (PKs). We present a new biomathematical approach that allows prediction of repeat-dose (RD) brain target occupancy (TO) using occupancy data obtained after administration of a single dose (SD). A PET study incorporating a sequential adaptive design was conducted in 10 healthy male adults who underwent 4 PET scans with [(11)C]DASB ([(11)C]N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine): 1 at baseline, 2 after 20 mg SD of the 5-hydroxytryptamine transporter (5-HTT) inhibitor duloxetine, and 1 after 4 days daily administration of 20 mg duloxetine. An adaptive design was used to select optimal times after SD for measurement of occupancy. Both direct and indirect PK/TO models were fitted to the SD data to characterise the model parameters and then applied to a predicted RD duloxetine plasma time course to predict the 5-HTT occupancy after RD. Repeat-dose prediction from the indirect model (OC(50)=2.62±0.93 ng/mL) was significantly better (P<0.05) than that from the direct model (OC(50)=2.29±1.11 ng/mL). This approach increases the value of SD occupancy studies that are performed as part of first time in human drug development programmes by providing an estimate of the dose required to achieve the desired TO at RD.
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