Therapeutic Drug Monitoring of Vancomycin in Pediatric Patients With Extracorporeal Membrane Oxygenation Support.

OBJECTIVES: Determine pharmacokinetic (PK) parameters and optimal dosage of vancomycin for children on extracorporeal membrane oxygenation (ECMO). METHODS: Retrospective PK study of vancomycin in pediatric patients on ECMO who received IV vancomycin 40 to 60 mg/kg/day every 6 hours. Patients were analyzed according to the presence of acute kidney injury (AKI) and requirement of renal replacement therapy (RRT). RESULTS: Data from 40 children, with a median age of 2.7 years of age (1 month to 14 years) were evaluated. Thirty-two patients (80%) received vancomycin. Vancomycin therapeutic drug monitoring was performed in 29 patients. The subgroup without AKI or RRT were 15. With initial doses, vancomycin trough levels were within therapeutic range in 53% of patients. After dose change, 93% of patients achieved therapeutic levels. The adjusted dose was 40 (34-60) mg/kg/day every 6 hours. Estimated PK parameters were clearance (CL) 1.67 (1-1.67) mL/kg/min; volume of distribution (Vd) 0.73 (0.7-0.9) L/kg; and half-life (t½) 6.2 (4.9-8.06) hours. In the AKI subgroup, 11 patients, the initial median dose was 40 (30-45) mg/kg/day every 8 (6-12) hours. Trough concentrations of vancomycin were within therapeutic range in 27% of patients. After dose modifications, 63% of patients achieved target trough concentration. The final adjusted dose was 20 mg/kg/day (15-30) every 12 (12-24) hours. Estimated PK parameters were Vd 1.16 (0.68-1.6) L/kg; CL 0.83 (0.38-1) mL/kg/min; and a t½ of 23.6 (16.2-31) hours. CONCLUSIONS: In patients without AKI or RRT, Vd of vancomycin was similar and CL was lower compared to pediatric critically ill patients without ECMO. Treatment could be started at 40 mg/kg/day every 6 hours. In patients with AKI, the use of lower doses should be used.

[Therapeutic monitoring of vancomycin in critical care pediatric patients]. / Monitoreo terapéutico de vancomicina en una terapia intensiva pediátrica.

INTRODUCTION: Vancomycin is used in pediatric patients usually at 40 mg/kg/day four times daily. Recent data demonstrated the need of large doses to reach therapeutic concentrations in critical patients. OBJECTIVE: Describe dosage regime of vancomycin in patients from a pediatric intensive care unit, register values of plasmatic concentrations and determine the regimes necessary to reach therapeutic troughs. POPULATION, MATERIALS AND METHODS: We made an observational, retrospective study. Patients who received vancomycin by more than two days where studied. Patients who didn't register vancomycin troughs (minimum values) and/or with elevated serum creatinine were excluded. The age, grouping in younger than (<) 2 years and older than (>) 2 years and troughs of vancomycin were registered. Volume of distribution (Vd) and half-life (t 1/2) were obtained. Results. We studied 97 patients. Patients with undetectable plasmatic concentrations younger than two years were 14 and the older ones were 9, this difference was not statistically significant (p= 0.063). Mediam of the regime of administration for the younger group was 50 mg/kg/day each 6 h and for the older 40 mg/kg/day four times a day. Mediam (range) of Vd and half-life (t 1/2) for the group of < 2 years and >2 years were 0.682 (0.504-1.06) L/kg, 6.12 (2.66-17.49) h; 0.685 (0.389-1.198) L/kg, 4.88 (3.59-15.4) h, without significant differences. CONCLUSIONS: Dosage regime required an increase in frequency, in addition there were no significant differences between pharmacokinetic parameters and final administration regime for both groups, being able to suppose that equal schemes of administration could be implemented more frequently.

Monitoreo terapéutico de vancomicina en una terapia intensiva pediátrica / Therapeutic monitoring of vancomycin in critical care pediatric patients

Introducción. La vancomicina suele emplearse enpediatría a 40 mg/kg/día cada 6 h. Datos recienteshan demostrado la necesidad de dosis mayorespara alcanzar concentraciones terapéuticas en pacientescríticos.Objetivos. Describir los esquemas de dosificaciónde vancomicina en pacientes de una terapiaintensiva pediátrica, registrar los valores de lasconcentraciones plasmáticas y determinar los regímenesde dosificación necesarios para alcanzarvalles terapéuticos.Población, material y métodos. Realizamos un estudioobservacional, retrospectivo.Se estudiaron los pacientes que recibieron vancomicinapor más de dos días.Fueron excluidos quiénes no registraron valles (valoresmínimos) de vancomicina o con creatininasérica elevada.Se registraron: la edad, agrupándose en menores ymayores de 2 años, y los valles de vancomicina.Se obtuvieron: el volumen de distribución (Vd) y lasemivida plasmática (t 1/2).Resultados. Se estudiaron 97 pacientes. Los pacientescon dosaje indetectable menores de dos añosfueron 14 y los mayores 9 (p= 0,063).La mediana del régimen de dosificación para losgrupos de menor edad y mayor edad fue de 50mg/kg/día cada 6 h y 40 mg/kg/día cada 6 h,respectivamente.Las medianas (intervalo) del Vd y t 1/2 para losmenores de 2 años y mayores de 2 años fueron0,682 (0,504-1,06) L/kg, 6,12 (2,66-17,49) h; 0,685(0,389-1,198) L/kg, 4,88 (3,59-15,4) h, sin diferenciassignificativas.Conclusiones. Los esquemas de dosificación requirieronun aumento de frecuencia; además, no seencontraron diferencias significativas entre losparámetros farmacocinéticos y esquemas finales dedosificación para ambos grupos, lo cual habilita asuponer que podrían implementarse iguales esquemasde dosificación con una frecuencia mayor.

Introduction. Vancomycin is used in pediatric patients usually at 40 mg/kg/day four times daily. Recent data demonstrated the need of large doses to reach therapeutic concentrations in critical patients. Objective. Describe dosage regime of vancomycin in patients from a pediatric intensive care unit register values of plasmatic concentrations and determine the regimes necessary to reach therapeutic troughs. Population, materials and methods. We made an observational, retrospective study. Patients who received vancomycin by more than two days where studied. Patients who didn’t register vancomycin troughs (minimum values) and/or with elevated serum creatinine were excluded. The age, grouping in younger than (<) 2 years and older than (>) 2 years and troughs of vancomycin were registered. Volume of distribution (Vd) and half-life (t 1/2) were obtained. Results. We studied 97 patients. Patients with undetectable plasmatic concentrations younger than two years were 14 and the older ones were 9, this difference was not statistically significant (p= 0.063). Mediam of the regime of administration for the younger group was 50 mg/kg/day each 6 h and for the older 40 mg/kg/day four times a day. Mediam (range) of Vd and half-life (t 1/2) for the group of < 2 years and >2 years were 0.682 (0.504-1.06) L/kg, 6.12 (2.66-17.49) h; 0.685 (0.389-1.198) L/kg, 4.88 (3.59-15.4) h, without significant differences. Conclusions. Dosage regime required an increase in frequency, in addition there were no significant differences between pharmacokinetic parameters and final administration regime for both groups, being able to suppose that equal schemes of administration could be implemented more frequently.

Desarrollo y Estabilidad de Sulfato de Indinavil en una formulación Oral Pediátrica / Development and stability of indinavir sulfate in a pediatric oral formulation

Se estudió estabilidad del sulfato de indinavir en un liquido oral extemporáneo almacenado a 4ºC, 25ºC y 37º C. Una solución concentrada fue preparada de cápsulas disponibles en el comercio del sulfato del indinavir, y después diluida con un vehiculo adecuado, para obtener una concentración final de 20 mg/mL. El liquido fue dividido en tres envases de vidrio color caramelo de 30 ML y almacenado a 4ºC, 25ºC y 37ºC. El contenido de sulfato del indinavir de cada uno de los tres envases fue ensayado por cromatografía líquida de alta performance (HPLC). Cada muestra fue ensayada por triplicado a tiempo O y a los 1, 7, 14, 30, 45, 60 días. Las muestras, además fueron observadas visualmente y fue medido el pH. La concentración de sulfato del indinavir excedió el 95% de la concentración inicial a 4ºC por 45 días, a 25ºC por 30 días y a 37ºC por 7 días. El sulfato de indinavir, 20 mg/mL en un liquido oral extemporáneo, fue estable a 4ºC, 45 días; a 25ºC, 30 días y 7 días a 37ºC.