Trial reportEuropean journal of nuclear medicine and molecular imaging2008
Peripheral metabolism of (R)-[11C]verapamil in epilepsy patients.
Trial report in European journal of nuclear medicine and molecular imaging, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Effect of P-glycoprotein inhibition at the blood-brain barrier on brain distribution of (R)-[British journal of clinical pharmacology · 2017Trial
- A combined accelerator mass spectrometry-positron emission tomography human microdose study with 14C- and 11C-labelled verapamil.Clinical pharmacokinetics · 2011Trial
- A pilot study to assess the efficacy of tariquidar to inhibit P-glycoprotein at the human blood-brain barrier with (R)-11C-verapamil and PET.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2009Trial
- Designing a Small Molecule for PET Radiotracing: [Molecules (Basel, Switzerland) · 2025Review
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- [Fluids and barriers of the CNS · 2024Article
- Performance and Sensitivity of [Molecular pharmaceutics · 2024Article
- Impact of Cytochrome Induction or Inhibition on the Plasma and Brain Kinetics of [Pharmaceutics · 2022Article
- Using positron emission tomography to study transporter-mediated drug-drug interactions in tissues.Clinical pharmacology and therapeutics · 2014Review
- PET radiopharmaceuticals for probing enzymes in the brain.American journal of nuclear medicine and molecular imaging · 2013Article
- Interaction of HM30181 with P-glycoprotein at the murine blood-brain barrier assessed with positron emission tomography.European journal of pharmacology · 2012Article
- Synthesis and preclinical evaluation of the radiolabeled P-glycoprotein inhibitor [(11)C]MC113.Nuclear medicine and biology · 2012Article
- The antiepileptic drug mephobarbital is not transported by P-glycoprotein or multidrug resistance protein 1 at the blood-brain barrier: a positron emission tomography study.Epilepsy research · 2012Article
- Pgp-mediated interaction between (R)-[11C]verapamil and tariquidar at the human blood-brain barrier: a comparison with rat data.Clinical pharmacology and therapeutics · 2012Article
- PET and SPECT radiotracers to assess function and expression of ABC transporters in vivo.Current drug metabolism · 2011Review
- A novel positron emission tomography imaging protocol identifies seizure-induced regional overactivity of P-glycoprotein at the blood-brain barrier.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
- Dose-response assessment of tariquidar and elacridar and regional quantification of P-glycoprotein inhibition at the rat blood-brain barrier using (R)-[(11)C]verapamil PET.European journal of nuclear medicine and molecular imaging · 2010Article
- Assessment of regional differences in tariquidar-induced P-glycoprotein modulation at the human blood-brain barrier.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2010Article
- Imaging of P-glycoprotein function and expression to elucidate mechanisms of pharmacoresistance in epilepsy.Current topics in medicinal chemistry · 2010Review
- Synthesis and small-animal positron emission tomography evaluation of [11C]-elacridar as a radiotracer to assess the distribution of P-glycoprotein at the blood-brain barrier.Journal of medicinal chemistry · 2009Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purpose(R)-[(11)C]verapamil is a new PET tracer for P-glycoprotein-mediated transport at the blood-brain barrier. For kinetic analysis of (R)-[(11)C]verapamil PET data the measurement of a metabolite-corrected arterial input function is required. The aim of this study was to assess peripheral (R)-[(11)C]verapamil metabolism in patients with temporal lobe epilepsy and compare these data with previously reported data from healthy volunteers.
methodsArterial blood samples were collected from eight patients undergoing (R)-[(11)C]verapamil PET and selected samples were analysed for radiolabelled metabolites of (R)-[(11)C]verapamil by using an assay that measures polar N-demethylation metabolites by solid-phase extraction and lipophilic N-dealkylation metabolites by HPLC.
resultsPeripheral metabolism of (R)-[(11)C]verapamil was significantly faster in patients compared to healthy volunteers (AUC of (R)-[(11)C]verapamil fraction in plasma: 29.4 +/- 3.9 min for patients versus 40.8 +/- 5.0 min for healthy volunteers; p < 0.0005, Student's t-test), which resulted in lower (R)-[(11)C]verapamil plasma concentrations (AUC of (R)-[(11)C]verapamil concentration, normalised to injected dose per body weight: 25.5 +/- 2.1 min for patients and 30.5 +/- 5.9 min for healthy volunteers; p = 0.038). Faster metabolism appeared to be mainly due to increased N-demethylation as the polar [(11)C]metabolite fraction was up to two-fold greater in patients.
conclusionsFaster metabolism of (R)-[(11)C]verapamil in epilepsy patients may be caused by hepatic cytochrome P450 enzyme induction by antiepileptic drugs. Based on these data caution is warranted when using an averaged arterial input function derived from healthy volunteers for the analysis of patient data. Moreover, our data illustrate how antiepileptic drugs may decrease serum levels of concomitant medication, which may eventually lead to a loss of therapeutic efficacy.
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