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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-01-2008 | Original Article

Peripheral metabolism of (R)-[¹¹C]verapamil in epilepsy patients

Authors: 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

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 1/2008

Abstract

Purpose

(R)-[¹¹C]verapamil is a new PET tracer for P-glycoprotein-mediated transport at the blood-brain barrier. For kinetic analysis of (R)-[¹¹C]verapamil PET data the measurement of a metabolite-corrected arterial input function is required. The aim of this study was to assess peripheral (R)-[¹¹C]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)-[¹¹C]verapamil PET and selected samples were analysed for radiolabelled metabolites of (R)-[¹¹C]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)-[¹¹C]verapamil was significantly faster in patients compared to healthy volunteers (AUC of (R)-[¹¹C]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)-[¹¹C]verapamil plasma concentrations (AUC of (R)-[¹¹C]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 [¹¹C]metabolite fraction was up to two-fold greater in patients.

Conclusions

Faster metabolism of (R)-[¹¹C]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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Title: Peripheral metabolism of (R)-[11C]verapamil in epilepsy patients
Authors: 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
Publication date: 01-01-2008
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 1/2008
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-007-0556-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Peripheral metabolism of (R)-[¹¹C]verapamil in epilepsy patients

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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