Analysis of Vancomycin Dosage and Plasma Levels in Critically Ill Adult Patients Requiring Extracorporeal Membrane Oxygenation (ECMO).

Introduction: Critically ill patients undergoing extracorporeal membrane oxygenation (ECMO) exhibit unique pharmacokinetics. This study aimed to assess the achievement of vancomycin therapeutic targets in these patients. Methods: This retrospective cohort study included patients on ECMO treated with vancomycin between January 2010 and December 2018. Ninety patients were analyzed based on ECMO connection modality, baseline creatinine levels, estimated glomerular filtration rate (eGFR), renal replacement therapy (RRT) requirements, and vancomycin loading dose administration. Results: Twenty-three percent of the patients achieved the therapeutic range defined by baseline levels. No significant differences in meeting the therapeutic goal were found in multivariate analysis considering ECMO cannulation modality, initial creatinine level, initial eGFR, RRT requirement, or loading dose use. All trough levels between 15 and 20 mcg/mL achieved an estimated area under the curve/minimum inhibitory concentration (AUC/MIC) between 400 and 600, almost all trough levels over 10 mcg/mL predicted an AUC/MIC >400. Discussion: Achieving therapeutic plasma levels in these patients remains challenging, potentially due to factors such as individual pharmacokinetics and pathophysiology. A trough plasma level between 12 and 20 estimated the therapeutic AUC/MIC for all models, proposing a possible lower target, maintaining exposure, and potentially avoiding adverse effects. Despite being one of the largest cohorts of vancomycin use in ECMO patients studied, its retrospective nature and single-center focus limits its broad applicability.

Population Pharmacokinetics of Vancomycin and Meropenem in Pediatric Extracorporeal Membrane Oxygenation Support.

Objective: Describe primary pharmacokinetic/pharmacodynamic (PK/PD) parameters of vancomycin and meropenem in pediatric patients undergoing ECMO and analyze utilized dosing to reach PK/PD target. Design: Prospective, multicentric, population PK analysis. Setting: Two hospitals with pediatric intensive care unit. Patients: Pediatric patients (1 month - 15 years old) receiving vancomycin and meropenem for empiric or definitive infection treatment while ECMO support. Measurements and Main Results: Four serum concentration were obtained for patients receiving vancomycin (n = 9) and three for meropenem (n = 9). The PK/PD target for vancomycin was a ratio of the area under the curve to the minimal inhibitory concentration (AUC/MIC) of >400, and for meropenem was 4 times above MIC for 50% of the dosing interval (fT50% > 4xMIC). Pharmacokinetic modeling was performed using PMetrics 1.5.0. We included nine patients, with 11 PK profiles for each antimicrobial. The median age of patients was 4 years old (2 months - 13 years) and 45% were male. Creatinine clearance (CL) was 183 (30-550) ml/min/1.73 m2. The median dose was 13.6 (range 10-15) mg/kg every 6-12 h and 40 mg/kg every 8-12 h for vancomycin and meropenem, respectively. Two compartment models were fitted. Weight was included as a covariate on volume of the central compartment (Vc) for meropenem. Weight was included as a covariate on both Vc and clearance (CL) and serum creatinine was also included as a covariate on CL for vancomycin. The pharmacokinetic parameters CL and Vc were 0.139 ± 0.102 L/h/kg and 0.289 ± 0.295 L/kg for meropenem and 0.060 ± 0.055 L/h/kg and 0.419 ± 0.280 L/kg for vancomycin, respectively. Across each dosing interval 91% of patients achieved the PK/PD targets for adequate exposure for meropenem and 63.6% for vancomycin. Conclusion: Pharmacokinetic/pharmacodynamic objectives for vancomycin were achieved partially with conventional doses and higher dosing with extended infusion were needed in the case of meropenem.

[Plasmatic concentracion of piperacillin/tazobactam in pediatric patients on ECMO support. Preliminary analysis]. / Concentraciones plasmáticas de piperacilina/tazobactam en pacientes pediátricos críticos sometidos a ECMO. Análisis preliminar.

BACKGROUND: Pharmacokinetics and optimal dosing of piperacillin tazobactam (PT) have not been well studied in pediatric patients undergoing extracorporeal oxygenation membrane (ECMO). AIM: To describe piperacillin plasmatic concentration and evaluate achievement of pharmaccokinetic/pharmacodinamic objective in patients on ECMO support. METHOD: We report three pediatric patients admitted to the Pediatric Intensive Care Unit, treated with PT undergoing ECMO. Plasmatic concentrations of piperacillin were obtained in the middle of the dosing interval using high performance liquid chromatography. RESULTS: Plasmatic concentrations were 51,7-14,1 and 6,5 µg/mL for patient A, B and C respectively. Only one patient reached adequate concentrations. CONCLUSION: These preliminary results suggest that availability of plasmatic concentrations of piperacillin could optimize the achievement of pharmacokinetic/pharmacodynamic objectives in pediatric patients on ECMO support.

Concentraciones plasmáticas de piperacilina/tazobactam en pacientes pediátricos críticos sometidos a ECMO: análisis preliminar / Plasmatic concentracion of piperacillin/tazobactam in pediatric patients on ECMO support: preliminary analysis

Resumen Introducción: Se desconocen las alteraciones farmacocinéticas de piperacilina/tazobactam (PT) en pacientes pediátricos que requieren de membrana de oxigenación extracorpórea (ECMO) y cómo dosificar adecuadamente dicho antimicrobiano. Objetivo: Describir las concentraciones plasmáticas (CP)y evaluar el cumplimiento del objetivo farmacocinético/famacodinámico de piperacilina en pacientes pediátricos en soporte con ECMO. Métodos: Presentamos tres pacientes pediátricos en tratamiento con PT que requirieran de ECMO en los que se midieron CP de piperacilina en la mitad del intervalo de dosificación mediante cromatografía liquida de alta resolución. Resultados: Las CP fueron 51,7-14,1 y 6,5 μg/mL para los pacientes A, B y C, respectivamente. Sólo se alcanzaron CP adecuadas en un paciente. Conclusión: Estos resultados preliminares sugieren que la disponibilidad de CP de piperacilina podría optimizar el cumplimiento de los objetivos farmacocinéticos/farmacodinámicos en pacientes pediátricos en soporte con ECMO.

Abstract Background: Pharmacokinetics and optimal dosing of piperacillin tazobactam (PT) have not been well studied in pediatric patients undergoing extracorporeal oxygenation membrane (ECMO). Aim: To describe piperacillin plasmatic concentration and evaluate achievement of pharmaccokinetic/pharmacodinamic objective in patients on ECMO support. Method: We report three pediatric patients admitted to the Pediatric Intensive Care Unit, treated with PT undergoing ECMO. Plasmatic concentrations of piperacillin were obtained in the middle of the dosing interval using high performance liquid chromatography. Results: Plasmatic concentrations were 51,7-14,1 and 6,5 μg/mL for patient A, B and C respectively. Only one patient reached adequate concentrations. Conclusion: These preliminary results suggest that availability of plasmatic concentrations of piperacillin could optimize the achievement of pharmacokinetic/pharmacodynamic objectives in pediatric patients on ECMO support.

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 antimicrobial agents in pediatrics. Review based on Latin American experiences]. / Monitorización terapéutica de antimicrobianos en pediatría. Revisión de la experiencia latinoamericana.

This review summarizes recommendations of therapeutic monitoring of three antimicrobials based in regional data: vancomycin, amikacin and voriconazole in pediatric population. Regional evidence agrees with international literature regarding the requirement of higher daily doses than 40 mg/kg/day of vancomycin, as well as with the possibility of use one daily doses of amikacin and to recommend higher doses of voriconazole compared to the initially recommended doses of 8 mg/kg/day. Local data on the pharmacokinetic/pharmacodynamic behavior of various antimicrobials in pediatrics are of great value for dosing adjustment in our pediatric population. More studies in therapeutic monitoring in the use of antimicrobials in pediatrics should be performed in order to allow the generation of adequate treatment guidelines for this age group.

Monitorización terapéutica de antimicrobianos en pediatría: revisión de la experiencia latinoamericana / Therapeutic monitoring of antimicrobial agents in pediatrics: review based on Latin American experiences

Resumen La presente revisión resume la evidencia sobre la monitorización terapéutica de tres antimicrobianos basada en datos regionales: vancomicina, amikacina y voriconazol en la población pediátrica. Estos datos coinciden con la literatura internacional en relación al requerimiento de dosis mayores que 40 mg/kg/día de vancomicina, la posibilidad de usar monodosis diarias de amikacina y el requerimiento de dosis mayores de voriconazol en relación a las iniciales recomendadas de 8 mg/kg/día. Contar con datos locales sobre el comportamiento farmacocinético/farmacodinámico de diversos antimicrobianos en la pediatría es de gran valor para adecuar la dosificación de los mismos en nuestra población. Se deberían incrementar los estudios de monitorización terapéutica en el uso de antimicrobianos en pediatría que permitan generar pautas de tratamiento adecuadas para este grupo etario.

This review summarizes recommendations of therapeutic monitoring of three antimicrobials based in regional data: vancomycin, amikacin and voriconazole in pediatric population. Regional evidence agrees with international literature regarding the requirement of higher daily doses than 40 mg/kg/day of vancomycin, as well as with the possibility of use one daily doses of amikacin and to recommend higher doses of voriconazole compared to the initially recommended doses of 8 mg/kg/day. Local data on the pharmacokinetic/pharmacodynamic behavior of various antimicrobials in pediatrics are of great value for dosing adjustment in our pediatric population. More studies in therapeutic monitoring in the use of antimicrobials in pediatrics should be performed in order to allow the generation of adequate treatment guidelines for this age group.

[Continuous infusion of vancomycin in pediatric critical care]. / Vancomicina en infusión continua en pacientes pediátricos críticos.

Continuous infusion of vancomycin may be a strategy for critically ill patients who do not achieve adequate plasma levels. There is few literature on this dosage regimen. We present six children (2 months to 7 years, 4 male and 2 female), admitted to the Intensive Care Unit of the "Prof. Dr. Garrahan Children Hospital", with methicillin-resistant Staphylococcus aureus sepsis, treated with vancomycin 40 and 60 mg/kg/day every 8-6 hrs. Continuous infusion at 50 mg/kg/day was implemented due to poor outcome, persistent fever, positive cultures and inadequate vancomycin plasma levels. All patients achieved levels between 10 and 25 ug/ml, their outcome was favorable and cultures became negative, with no signs of nephrotoxicity. Treatment duration of the continuous infusion was 9 to 18 days. Continuous infusion of vancomycin was effective in these patients without evidence of associated nephrotoxicity.

Vancomicina en infusión continua en pacientes pediátricos críticos / Continuous infusion of vancomycin in pediatric critical care

La administración de vancomicina en infusión continua es una estrategia de tratamiento posible en pacientes críticos que no alcancen niveles plasmáticos adecuados. Existe escasa bibliografía acerca de este tipo de administración. Se presentan 6 niños (2 meses a 7 años; 4 varones y 2 mujeres) que ingresaron en la unidad de cuidados intensivos del Hospital de Pediatría Garrahan con un cuadro clínico de sepsis por Staphylococcus aureus resistente a la meticilina, tratados con vancomicina, en dosis de entre 40 y 60 mg/kg/día cada 8-6 horas. Debido a la evolución clínica no favorable, la persistencia de la fiebre, los cultivos positivos y los niveles plasmáticos del antibiótico insuficientes, se implementó la infusión continua a 50 mg/kg/día. Todos los pacientes alcanzaron niveles entre 10 y 25 µg/ml, evolucionaron favorablemente y negativizaron los cultivos, sin signos de nefrotoxicidad. El tiempo de tratamiento en infusión continua fue entre 9 y 18 días. La infusión continua de vancomicina fue eficaz en estos pacientes, sin evidencias de nefrotoxicidad asociada.

Continuous infusion of vancomycin may be a strategy for critically ill patients who do not achieve adequate plasma levels. There is few literature on this dosage regimen. We present six children (2 months to 7 years, 4 male and 2 female), admitted to the Intensive Care Unit of the "Prof. Dr. Garrahan Children Hospital", with methicillin-resistant Staphylococcus aureus sepsis, treated with vancomycin 40 and 60 mg/kg/day every 8-6 hrs. Continuous infusion at 50 mg/kg/day was implemented due to poor outcome, persistent fever, positive cultures and inadequate vancomycin plasma levels. All patients achieved levels between 10 and 25 ug/ml, their outcome was favorable and cultures became negative, with no signs of nephrotoxicity. Treatment duration of the continuous infusion was 9 to 18 days. Continuous infusion of vancomycin was effective in these patients without evidence of associated nephrotoxicity.

Vancomicina en infusión continua en pacientes pediátricos críticos / Continuous infusion of vancomycin in pediatric critical care

La administración de vancomicina en infusión continua es una estrategia de tratamiento posible en pacientes críticos que no alcancen niveles plasmáticos adecuados. Existe escasa bibliografía acerca de este tipo de administración. Se presentan 6 niños (2 meses a 7 años; 4 varones y 2 mujeres) que ingresaron en la unidad de cuidados intensivos del Hospital de Pediatría Garrahan con un cuadro clínico de sepsis por Staphylococcus aureus resistente a la meticilina, tratados con vancomicina, en dosis de entre 40 y 60 mg/kg/día cada 8-6 horas. Debido a la evolución clínica no favorable, la persistencia de la fiebre, los cultivos positivos y los niveles plasmáticos del antibiótico insuficientes, se implementó la infusión continua a 50 mg/kg/día. Todos los pacientes alcanzaron niveles entre 10 y 25 Ag/ml, evolucionaron favorablemente y negativizaron los cultivos, sin signos de nefrotoxicidad. El tiempo de tratamiento en infusión continua fue entre 9 y 18 días. La infusión continua de vancomicina fue eficaz en estos pacientes, sin evidencias de nefrotoxicidad asociada.(AU)

Continuous infusion of vancomycin may be a strategy for critically ill patients who do not achieve adequate plasma levels. There is few literature on this dosage regimen. We present six children (2 months to 7 years, 4 male and 2 female), admitted to the Intensive Care Unit of the "Prof. Dr. Garrahan Children Hospital", with methicillin-resistant Staphylococcus aureus sepsis, treated with vancomycin 40 and 60 mg/kg/day every 8-6 hrs. Continuous infusion at 50 mg/kg/day was implemented due to poor outcome, persistent fever, positive cultures and inadequate vancomycin plasma levels. All patients achieved levels between 10 and 25 ug/ml, their outcome was favorable and cultures became negative, with no signs of nephrotoxicity. Treatment duration of the continuous infusion was 9 to 18 days. Continuous infusion of vancomycin was effective in these patients without evidence of associated nephrotoxicity.(AU)

Vancomicina en infusión continua en pacientes pediátricos críticos. / [Continuous infusion of vancomycin in pediatric critical care].

Continuous infusion of vancomycin may be a strategy for critically ill patients who do not achieve adequate plasma levels. There is few literature on this dosage regimen. We present six children (2 months to 7 years, 4 male and 2 female), admitted to the Intensive Care Unit of the "Prof. Dr. Garrahan Children Hospital", with methicillin-resistant Staphylococcus aureus sepsis, treated with vancomycin 40 and 60 mg/kg/day every 8-6 hrs. Continuous infusion at 50 mg/kg/day was implemented due to poor outcome, persistent fever, positive cultures and inadequate vancomycin plasma levels. All patients achieved levels between 10 and 25 ug/ml, their outcome was favorable and cultures became negative, with no signs of nephrotoxicity. Treatment duration of the continuous infusion was 9 to 18 days. Continuous infusion of vancomycin was effective in these patients without evidence of associated nephrotoxicity.

[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.

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.(AU)

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 didnãt 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.(AU)

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.

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. (AU)