Patsalos, PN;
Zugman, M;
Lake, C;
James, A;
Ratnaraj, N;
Sander, JW;
(2017)
Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: A comparison of free non-protein-bound concentrations.
Epilepsia
, 58
(7)
pp. 1234-1243.
10.1111/epi.13802.
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Abstract
Objective Given that only the free non–protein-bound concentration of an antiepileptic drug (AED) crosses the blood–brain barrier, entering the brain and producing an antiepileptic effect, knowledge and measurement of the free drug fraction is important. Such data are sparse, particularly for newer AEDs, and have arisen from the use of disparate methodologies and settings over the past six decades. We report on the protein binding of 25 AEDs that are available for clinical use, along with two pharmacologically active metabolites (carbamazepine-epoxide and N-desmethyl clobazam), using standardized methodology and under set conditions. Methods The protein binding of the various AEDs was undertaken in sera of 278 patients with epilepsy. Separation of the free non–protein-bound component was achieved by using ultracentrifugation (Amicon Centrifree Micropartition System) under set conditions: 500 μl serum volume; centrifugation at 1,000 g for 15 min, and at 25°C. Free and total AED concentrations were measured by use of fully validated liquid chromatography/mass spectroscopy (LC/MS) techniques. Results Gabapentin and pregabalin are non–protein-bound, whereas highly bound AEDs (≥88%) include clobazam, clonazepam, perampanel, retigabine, stiripentol, tiagabine, and valproic acid as well as the N-desmethyl-clobazam (89%) metabolite. The minimally bound drugs (<22%) include ethosuximide (21.8%), lacosamide (14.0%), levetiracetam (3.4%), topiramate, (19.5%) and vigabatrin (17.1%). Ten of the 25 AEDs exhibit moderate protein binding (mean range 27.7–74.8%). Significance These data provide a comprehensive comparison of serum protein binding of all available AEDs including the metabolites, carbamazepine-epoxide and N-desmethyl-clobazam. Knowledge of the free fraction of these AEDs can be used to optimize epilepsy treatment.
| Type: | Article |
|---|---|
| Title: | Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: A comparison of free non-protein-bound concentrations |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/epi.13802 |
| Publisher version: | http://doi.org/10.1111/epi.13802 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences & Neurology, Ultracentrifugation, Free fraction, New antiepileptic drugs, Therapeutic drug monitoring, Epilepsy treatment, VALPROIC ACID, EPILEPTIC PATIENTS, PLASMA-CONCENTRATIONS, HEALTHY-SUBJECTS, PHENYTOIN, SALIVA, PHARMACOKINETICS, CARBAMAZEPINE, METABOLISM, OXCARBAZEPINE |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1558511 |
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