| Literature DB >> 32461746 |
Katherine E Hamilton, Chasity M Shelton, James Wheless, Stephanie J Phelps.
Abstract
We describe an 11-year-old female who presented with severe hypersomnolence after receiving 1 week of modest doses of clobazam (CLB). In reviewing the above case, we considered that the hypersomnolence could be related to a pharmacodynamic, pharmacokinetic, or pharmacogenomic issue associated with CLB or to a combination of these factors. Although serum concentrations of CLB and its active metabolite are sensitive to factors that affect cytochrome-dependent metabolism, drug-drug interactions were omitted as a cause of the hypersomnolence. Subsequent DNA analysis of the cytochrome P450 2C19 gene revealed the patient as *2/*2 genotype with poor metabolizer enzyme activity. Because genetic testing of all patients treated with CLB is currently not practical, CLB dose/concentration ratios and pharmacokinetic drug-drug interaction impact models may be indicated. Genetic testing should be considered when an adverse effect suggests the possibility of a polymorphism important to drug metabolism. Copyright Pediatric Pharmacy Association. All rights reserved. For permissions, email: mhelms@pediatricpharmacy.org 2020.Entities:
Keywords: CYP2C19; NCLB, pharmacogenomics; adverse drug effect; clobazam; hypersomnolence; polymorphism
Year: 2020 PMID: 32461746 PMCID: PMC7243903 DOI: 10.5863/1551-6776-25.4.320
Source DB: PubMed Journal: J Pediatr Pharmacol Ther ISSN: 1551-6776