A Case-report of Unpredictable and Massive Voriconazole Intoxication in a Patient with Extensive CYP2C19 and CYP2C9 Polymorphisms
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- LEMAITRE Florian
- Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital Laboratory of Experimental and Clinical Pharmacology, Faculty of Medicine, Rennes 1 University Clinical Investigation Center, CIC-P 0203, INSERM EA4123 Barrières Physiologiques et Réponses Thérapeutiques, Faculty of Pharmacy, Paris XI University
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- BARBAZ Mathilde
- Department of Infectious Diseases and Medical Intensive Care, Rennes University Hospital
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- SCAILTEUX Lucie-Marie
- Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital
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- UHEL Fabrice
- Clinical Investigation Center, CIC-P 0203, INSERM Department of Infectious Diseases and Medical Intensive Care, Rennes University Hospital
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- TADIÉ Jean-Marc
- Clinical Investigation Center, CIC-P 0203, INSERM Department of Infectious Diseases and Medical Intensive Care, Rennes University Hospital
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- VERDIER Marie-Clémence
- Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital Laboratory of Experimental and Clinical Pharmacology, Faculty of Medicine, Rennes 1 University Clinical Investigation Center, CIC-P 0203, INSERM
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- BELLISSANT Eric
- Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital Laboratory of Experimental and Clinical Pharmacology, Faculty of Medicine, Rennes 1 University Clinical Investigation Center, CIC-P 0203, INSERM
書誌事項
- タイトル別名
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- A Case-report of Unpredictable and Massive Voriconazole Intoxication in a Patient with Extensive <i>CYP2C19</i> and <i>CYP2C9</i> Polymorphisms
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抄録
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.<br>
収録刊行物
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- Ｄｒｕｇ Ｍｅｔａｂｏｌｉｓｍ ａｎｄ Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ
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Ｄｒｕｇ Ｍｅｔａｂｏｌｉｓｍ ａｎｄ Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ 28 (5), 439-441, 2013
日本薬物動態学会