Impact of CYP2C19 Genotype and Drug Interactions on Voriconazole Plasma Concentrations: A Spain Pharmacogenetic-Pharmacokinetic Prospective Multicenter Study
| Autor: | Dolores Belles Medall, Francisco Javier Otero Espinar, María Jesús Lamas, Gema Barbeito Castiñeiras, Aurea Gómez Márquez, Andrés Blanco Hortas, Olalla Maroñas, Goretti Durán Piñeiro, Sara Blanco-Dorado, Belén Bardán García, Ana López-Vizcaíno, Anxo Fernández-Ferreiro, Angel Carracedo, Manuel Campos-Toimil, María Luisa Pérez del Molino Bernal, Irene Zarra Ferro, Ana Latorre-Pellicer, María Teresa Rodríguez Jato |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Antifungal Agents Drug-Related Side Effects and Adverse Reactions Genotype 030106 microbiology CYP2C19 030204 cardiovascular system & hematology Gastroenterology 03 medical and health sciences Route of administration 0302 clinical medicine Therapeutic index Pharmacokinetics Internal medicine Prevalence Medicine Humans Pharmacology (medical) Prospective Studies Adverse effect Voriconazole medicine.diagnostic_test Dose-Response Relationship Drug business.industry Cytochrome P-450 CYP2C19 Mycoses Therapeutic drug monitoring Spain Female Drug Monitoring business Pharmacogenetics medicine.drug |
| Zdroj: | PharmacotherapyReferences. 40(1) |
| ISSN: | 1875-9114 |
| Popis: | Background: Voriconazole, a first-line agent for the treatment of invasive fungal infections, is mainly metabolized by cytochrome P450 (CYP) 2C19. A significant portion of patients fail to achieve therapeutic voriconazole trough concentrations, with a consequently increased risk of therapeutic failure. Objective: To show the association between subtherapeutic voriconazole concentrations and factors affecting voriconazole pharmacokinetics: CYP2C19 genotype and drug–drug interactions. Methods: Adults receiving voriconazole for antifungal treatment or prophylaxis were included in a multicenter prospective study conducted in Spain. The prevalence of subtherapeutic voriconazole troughs was analyzed in the rapid metabolizer and ultra-rapid metabolizer patients (RMs and UMs, respectively), and compared with the rest of the patients. The relationship between voriconazole concentration, CYP2C19 phenotype, adverse events (AEs), and drug–drug interactions was also assessed. Results: In this study 78 patients were included with a wide variability in voriconazole plasma levels with only 44.8% of patients attaining trough concentrations within the therapeutic range of 1 and 5.5 µg/ml. The allele frequency of *17 variant was found to be 29.5%. Compared with patients with other phenotypes, RMs and UMs had a lower voriconazole plasma concentration (RM/UM: 1.85 ± 0.24 µg/ml vs other phenotypes: 2.36 ± 0.26 µg/ml). Adverse events were more common in patients with higher voriconazole concentrations (p |
| Databáze: | OpenAIRE |
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