| Clobazam therapeutic drug monitoring: a comprehensive review of the literature with proposals to improve future studies. | |
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MedLine Citation:
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PMID: 23318278 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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BACKGROUND: : Clobazam was recently approved for Lennox-Gastaut syndrome in the United States. There is no published review article focused on clobazam therapeutic drug monitoring (TDM) in English. METHODS: : More than 200 clobazam articles identified by a PubMed search were carefully reviewed for information on clobazam pharmacokinetics. Clobazam is mainly metabolized by a cytochrome P450 (CYP) isoenzyme, CYP3A4, to its active metabolite, N-desmethylclobazam. Then, N-desmethylclobazam is mainly metabolized by CYP2C19 unless the individual has no CYP2C19 activity [poor metabolizer (PM)]. RESULTS: : Using a mechanistic approach to reinterpret the published findings of steady-state TDM and single-dosing pharmacokinetic studies, 4 different serum clobazam concentration ratios were studied. The available limited steady-state TDM data suggest that the serum N-desmethylclobazam/clobazam ratio can be useful for clinicians, including identifying CYP2C19 PMs (ratio >25 in the absence of inhibitors). There are 3 possible concentration/dose (C/D) ratios. The clobazam C/D ratio has the potential to measure the contribution of CYP3A4 activity to the clearance of clobazam from the body. The N-desmethylclobazam C/D ratio does not seem to be a good measure of clobazam clearance and should be substituted with the total (clobazam + N-desmethylclobazam) C/D ratio. CONCLUSIONS: : Future clobazam TDM studies need to use trough concentrations after steady state has been reached (>3 weeks in normal individuals and several months in CYP2C19 PMs). These future studies need to explore the potential of clobazam and total C/D ratios. Better studies on the relative potency of N-desmethylclobazam compared with the parent compound are needed to provide weighted total serum concentrations that correct for the possible lower N-desmethylclobazam pharmacodynamic activity. Standardization and more studies of C/D ratios from clobazam and other drugs can be helpful to move TDM forward. |
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Authors:
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Jose de Leon; Edoardo Spina; Francisco J Diaz |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Therapeutic drug monitoring Volume: 35 ISSN: 1536-3694 ISO Abbreviation: Ther Drug Monit Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-01-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7909660 Medline TA: Ther Drug Monit Country: United States |
Other Details:
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Languages: eng Pagination: 30-47 Citation Subset: IM |
Affiliation:
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*University of Kentucky Mental Health Research Center at Eastern State Hospital, Lexington, Kentucky †Psychiatry and Neurosciences Research Group (CTS-549), Institute of Neurosciences, University of Granada, Granada, Spain ‡Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy §Department of Biostatistics, The University of Kansas Medical Center, Kansas City, Kansas. |
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