| Title: |
A Case-report of Unpredictable and Massive Voriconazole Intoxication in a Patient with Extensive CYP2C19 and CYP2C9 Polymorphisms. |
| Authors: |
Lemaitre, Florian; Barbaz, Mathilde; Scailteux, Lucie-Marie; Uhel, Fabrice; Tadié, Jean-Marc; Verdier, Marie-Clémence; Bellissant, Eric |
| Contributors: |
Service de Pharmacologie Rennes; Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou; Centre d'Investigation Clinique Rennes (CIC); Université de Rennes (UR)-Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou -Institut National de la Santé et de la Recherche Médicale (INSERM); Service des maladies infectieuses et réanimation médicale Rennes = Infectious Disease and Intensive Care Rennes |
| Source: |
ISSN: 1347-4367. |
| Publisher Information: |
HAL CCSD; Japanese Society for the Study of Xenobiotics |
| Publication Year: |
2013 |
| Collection: |
Université de Rennes 1: Publications scientifiques (HAL) |
| Subject Terms: |
voriconazole; N-oxide voriconazole; toxicology; pharmacokinetics; pharmacogenetics; therapeutic drug monitoring; neurotoxicity; [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences |
| Description: |
International audience ; This case-report describes a massive voriconazole (VRZ) intoxication in a patient with a poor metabolizer profile, highlighted by low plasma main metabolite concentrations (N-oxide voriconazole), despite an extensive genetic profile for CYP2C19 and CYP2C9. The patient was treated with a therapeutic dose of VRZ but developed a neurotoxicity leading to hallucinations and coma while the plasma concentration of VRZ reached an exceptional level (20.0 µg/mL on day 10 of the treatment). Since neurological disorders diminished in parallel with the decrease of VRZ plasma concentrations, the coma was likely due to VRZ. The VRZ half-life, calculated to 58 h in this patient, was by far higher than the values reported in the literature. While VRZ concentrations slowly decreased, the N-oxide voriconazole concentrations slowly increased from day 15. Hypotheses for this lack of metabolization of VRZ are an inhibition of the metabolism by esomeprazole, a saturation of the metabolism or an enzymatic auto-inhibition of VRZ metabolism but none of these hypotheses have yet been explored. This case-report of unpredictable accumulation of VRZ in a patient without any genetic risk factor is an advocacy for systematic therapeutic drug monitoring of VRZ. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/23545593; PUBMED: 23545593 |
| DOI: |
10.2133/dmpk.DMPK-13-NT-007 |
| Availability: |
https://univ-rennes.hal.science/hal-00910224; https://univ-rennes.hal.science/hal-00910224/document; https://univ-rennes.hal.science/hal-00910224/file/28_DMPK-13-NT-007.pdf; https://doi.org/10.2133/dmpk.DMPK-13-NT-007 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.295094BB |
| Database: |
BASE |