Evaluation of CYP2C19 Genotype-Guided Voriconazole Prophylaxis After Allogeneic Hematopoietic Cell Transplant.
Adult
Aged
Antifungal Agents
/ administration & dosage
Cost Savings
Cytochrome P-450 CYP2C19
/ genetics
Dose-Response Relationship, Drug
Female
Genotype
Hematopoietic Stem Cell Transplantation
Humans
Invasive Fungal Infections
/ etiology
Male
Middle Aged
Prospective Studies
Voriconazole
/ administration & dosage
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
05
06
2019
accepted:
22
07
2019
pubmed:
25
9
2019
medline:
29
10
2020
entrez:
25
9
2019
Statut:
ppublish
Résumé
There is a high risk of voriconazole failure in those with subtherapeutic drug concentrations, which is more common in CYP2C19 (cytochrome P450 2C19) rapid/ultrarapid metabolizers (RMs/UMs). We evaluated CYP2C19 genotype-guided voriconazole dosing on drug concentrations and clinical outcomes in adult allogeneic hematopoietic cell transplant recipients. Poor (PMs), intermediate (IMs), and normal metabolizers (NMs) received voriconazole 200 mg twice daily; RMs/UMs received 300 mg twice daily. Steady-state trough concentrations were obtained after 5 days, targeting 1.0-5.5 mg/L. Of 89 evaluable patients, 29% had subtherapeutic concentrations compared with 50% in historical controls (P < 0.001). Zero, 26%, 50%, and 16% of PMs, IMs, NMs, and RMs/UMs were subtherapeutic. Voriconazole success rate was 78% compared with 54% in historical controls (P < 0.001). No patients experienced an invasive fungal infection (IFI). Genotype-guided dosing resulted in $4,700 estimated per patient savings as compared with simulated controls. CYP2C19 genotype-guided voriconazole dosing reduced subtherapeutic drug concentrations and effectively prevented IFIs.
Substances chimiques
Antifungal Agents
0
CYP2C19 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP2C19
EC 1.14.14.1
Voriconazole
JFU09I87TR
Types de publication
Comparative Study
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
571-579Informations de copyright
© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.
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