Document Detail

Peripheral metabolism of (R)-[11C]verapamil in epilepsy patients.
MedLine Citation:
PMID:  17846766     Owner:  NLM     Status:  MEDLINE    
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. METHODS: Arterial 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. RESULTS: Peripheral 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. CONCLUSIONS: Faster 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.
Aiman Abrahim; Gert Luurtsema; Martin Bauer; Rudolf Karch; Mark Lubberink; Ekaterina Pataraia; Christian Joukhadar; Kurt Kletter; Adriaan A Lammertsma; Christoph Baumgartner; Markus Müller; Oliver Langer
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Publication Detail:
Type:  Clinical Trial; Journal Article     Date:  2007-09-11
Journal Detail:
Title:  European journal of nuclear medicine and molecular imaging     Volume:  35     ISSN:  1619-7089     ISO Abbreviation:  Eur. J. Nucl. Med. Mol. Imaging     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2007-12-07     Completed Date:  2009-03-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101140988     Medline TA:  Eur J Nucl Med Mol Imaging     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  116-23     Citation Subset:  IM    
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Währinger-Gürtel 18-20, 1090, Vienna, Austria.
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MeSH Terms
Calcium Channel Blockers / administration & dosage,  blood,  chemistry*,  metabolism*
Carbon Radioisotopes
Case-Control Studies
Chromatography, High Pressure Liquid
Epilepsy / blood,  metabolism*
Middle Aged
Solid Phase Extraction
Verapamil / administration & dosage,  blood,  chemistry*,  metabolism*
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Carbon Radioisotopes; 52-53-9/Verapamil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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