A multicentre prospective study evaluating the impact of proton-pump inhibitors omeprazole and pantoprazole on voriconazole plasma concentrations.

Voriconazole is an antifungal metabolised by CYP2C19 enzyme, which can be inhibited by proton-pump inhibitors (PPIs). A prospective observational study was carried out to determine the influence of PPIs on voriconazole pharmacokinetic. The 78 patients included were divided into 4 groups: omeprazole (n = 32), pantoprazole (n = 25), esomeprazole (n = 3) and no PPI (n = 18). Patients with no PPI had no significant difference in plasma voriconazole concentration when compared with those with PPI (2.63 ± 2.13 µg/mL [95% confidence interval {CI} 1.57-3.69] vs 2.11 ± 1.73 µg/mL [95%CI 1.67-2.55], P > .05). However, voriconazole plasma concentration was significantly lower in patients treated with pantoprazole vs those treated with omeprazole (1.44 ± 1.22 µg/mL [95%CI 0.94-1.94) vs 2.67 ± 1.88 µg/mL [95%CI 2.02-3.32], P = .013) suggesting a greater CYP2C19 enzyme inhibitory effect of omeprazole. This study demonstrates the greater CYP inhibition capacity of omeprazole and should be helpful for the choice of PPIs for patients treated with voriconazole.

Impact of CYP2C19 Genotype and Drug Interactions on Voriconazole Plasma Concentrations: A Spain Pharmacogenetic-Pharmacokinetic Prospective Multicenter Study.

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<0.05). No association between voriconazole trough concentration and other factors (age, weight, route of administration, and concomitant administration of enzyme inducer, enzyme inhibitor, glucocorticoids, or proton pump inhibitors) was found. CONCLUSION: These results suggest the potential clinical utility of using CYP2C19 genotype-guided voriconazole dosing to achieve concentrations in the therapeutic range in the early course of therapy. Larger studies are needed to confirm the impact of pharmacogenetics on voriconazole pharmacokinetics.

[Incidence of hypophosphatemia in not critically ill patients with enteral feeding]. / Incidencia de hipofosfatemia en pacientes ingresados no críticos con nutrición enteral.

BACKGROUND: Up to 30-40% of the patients starting artificial nutritional support develop hypophosphatemia. In general, patients with mild and moderate hypophosphatemia do not have symptoms, but severe hypophosphatemia is the hallmark of refeeding syndrome. AIM: To determine the incidence of hypophosphatemia in not critically ill patients receiving enteral feeding. MATERIAL AND METHODS: Prospective study. We assessed during seven days 181 not critically ill patients started on enteral artificial nutrition support during seven days. RESULTS: 51.9% of the patients were considered to be at risk of developing refeeding syndrome (United Kingdom National Institute for Health and Clinical Excellence criteria). The incidence of hypophosphatemia was 31.5%, but only 1.1% of the patients developed severe hypophosphatemia. Older age and lower plasma proteins were significantly associated with hypophosphatemia. CONCLUSION: The incidence of severe hypophosphatemia in our study is low, so we can't offer robust conclusions about the risk of hypophosphatemia in the type of patients receiving enteral nutrition.

INTRODUCCIÓN: se ha descrito una incidencia de hipofosfatemia en pacientes con soporte nutricional especializado (SNE) de hasta el 30-40%. La hipofosfatemia leve y la moderada son generalmente asintomáticas, mientras que la severa es el hecho fundamental del síndrome de realimentación. OBJETIVO: evaluar la incidencia y gravedad de la hipofosfatemia en pacientes hospitalizados no críticos con nutrición enteral (NE).MATERIAL Y MÉTODOS: se diseñó un estudio observacional y prospectivo en condiciones de práctica clínica habitual. Se recogieron datos clínicos, antropométricos y analíticos de 181 pacientes a los que se les inició nutrición enteral. El seguimiento fue de siete días.RESULTADOS: el 51,9% de los pacientes estaban en riesgo de desarrollar síndrome de realimentación según las guías del United Kingdom National Institute for Health and Clinical Excellence (NICE). La incidencia de hipofosfatemia fue del 31,5% y la de la hipofosfatemia severa, del 1,1%. De todos los parámetros clínicos, antropométricos y analíticos analizados, solo la edad y unas proteínas séricas más bajas se correlacionaron de forma estadísticamente significativa con el aumento en la incidencia de hipofosfatemia. CONCLUSIÓN: la incidencia de hipofosfatemia grave en nuestra serie es muy baja, lo que hace imposible extraer conclusiones específicas para este grupo de pacientes.