Physico-Chemical Stability of Admixtures of Vinflunine Used in Clinical Practice.

Procedure of administration of vinflunine is complex and consists of an Y-site injection with fluid at different speeds. Dose is diluted with 100 mL of 0.9% sodium chloride or 5% glucose and infused with half of the 500 mL bag of the fluid over 20 min; after that, the remaining fluid is administered at 300 mL/h. In this study, chemical stability and physical compatibility of vinflunine diluted with in 500 mL of both fluids were evaluated to simplify the administration procedure (infusion of mixture on 20 min followed by 250 mL of fluid at 300 mL/h). Physical compatibility and chemical stability were evaluated at two temperatures and protected from and exposed to light. Physical compatibility was evaluated by visual inspection, gravimetric control and measure of pH. A chromatographic method was developed to evaluate chemical stability. The dilution of vinflunine with 500 mL of fluid to final concentrations of 0.75 and 1.54 mg/mL is viable at doses used in clinical practice since admixtures are stable for 2 days at room temperature and at least 7 days under refrigeration. These results extend the expiration date of mixtures of vinflunine administered by the usual procedure and confirm the viability of the proposed procedure since administration is simplified and stability of vinflunine is guaranteed.

Clinical outcomes of the inclusion of the therapeutic drug monitoring report in the electronic clinical record / Resultados en salud de la integración del informe de monitorización farmacocinética en la historia clínica electrónica

Objectives: To assess the inclusion of the Therapeutic Drug Monitoring Report (TDMR) in the Electronic Clinical Record (ECR). Method: An observational ambispective cohort study with a duration of 149 days: PRE (retrospective, 49 days) with the TDMR printed in paper, and POST (prospective, 100 days) with the TDMR included in the ECR. Exclusion criteria: Patients not hospitalized, applications for Therapeutic Drug Monitoring by Critical Care and Neonatal Units, as well as monitoring with an objective other than dose adjustment. Variables: Number of TDMRs prepared, number of patients admitted with TDMR, time of delay for treatment adjustment, defined as the number of adjustments made to the treatment within over or under 24 hours from the time of TDMR preparation, and medication errors (MEs) associated with said delay, as well as the degree of acceptance of the TDMR. Results: 690 TDMRs were conducted in 391 patients, 339 in PRE (n = 206) and 351 in POST (n = 185). The number of treatment modifications made in under 24 hours increased from 73.9% in PRE to 87.3% in POST [RR = 1.2 (CI95% = 0.97-1.43). We identified 35 patients with ME, 9.7% of them in PRE and 8.1% in POST (RR = 0.84 (CI95% = 0.44-1.58)]. The degree of acceptance of the pharmacist recommendation increased from 53.3% in PRE to 68.3% in POST [RR = 1.3 (CI95% = 1.02- 1.62)]. Conclusions: The inclusion of the Therapeutic Drug Monitoring Report (TDMR) in the Electronic Clinical Record increases the degree of acceptance of recommendations, and may reduce the delay in treatment modifications, reducing MEs and improving the process quality in terms of efficacy and safety (AU)

Objetivos: Valorar la integración del informe de monitorización farmacocinética (IMFC) en la historia clínica electrónica (HCE). Método: Estudio observacional ambispectivo de cohortes de 149 días de duración: PRE (retrospectiva, 49 días) con emisión del IMFC en papel y POST (prospectiva, 100 días) con emisión del IMFC integrado en HCE. Criterios de exclusión: Pacientes no ingresados, solicitudes de monitorización farmacocinética de unidades de críticos y neonatos, así como monitorizaciones cuyo objetivo no era el ajuste posológico. Variables: Número de IMFC elaborados, número de pacientes ingresados con IMFC, tiempo de demora de las adecuaciones del tratamiento definidas como número de adecuaciones realizadas en el tratamiento en más o en menos 24 horas respecto al momento de emisión del IMFC, y errores de medicación (EM) asociados a dicha demora, así como grado de aceptación del IMFC. Resultados: Se realizaron 690 IFC en 391 pacientes, 339 en PRE (n = 206) y 351 en POST (n = 185). El número de modificaciones realizadas en menos de 24 horas aumentó del 73,9% en PRE al 87,3% en POST [RR = 1,2 (IC95% = 0,97-1,43)]. Se identificaron 35 pacientes con EM, siendo 9,7% en PRE y 8,1% en POST [RR = 0,84 (IC95% = 0,44-1,58)]. El grado de aceptación de la recomendación farmacéutica se incrementó de 53,3% en PRE a 68,3% en POST [RR = 1,3 (IC95% = 1,02-1,62)]. Conclusiones: La integración del informe de monitorización farmacocinética en la historia clínica electrónica incrementa el gra do de aceptación de las recomendaciones y puede disminuir la demora de las adecuaciones del tratamiento reduciendo los EM, mejorando con ello la calidad del proceso en eficacia y seguridad (AU)

Clinical outcomes of the inclusion of the therapeutic drug monitoring report in the electronic clinical record.

OBJECTIVES: To assess the inclusion of the Therapeutic Drug Monitoring Report (TDMR) in the Electronic Clinical Record (ECR). METHOD: An observational ambispective cohort study with a duration of 149 days: PRE (retrospective, 49 days) with the TDMR printed in paper, and POST (prospective, 100 days) with the TDMR included in the ECR. EXCLUSION CRITERIA: Patients not hospitalized, applications for Therapeutic Drug Monitoring by Critical Care and Neonatal Units, as well as monitoring with an objective other than dose adjustment. VARIABLES: Number of TDMRs prepared, number of patients admitted with TDMR, time of delay for treatment adjustment, defined as the number of adjustments made to the treatment within over or under 24 hours from the time of TDMR preparation, and medication errors (MEs) associated with said delay, as well as the degree of acceptance of the TDMR. RESULTS: 690 TDMRs were conducted in 391 patients, 339 in PRE (n = 206) and 351 in POST (n = 185). The number of treatment modifications made in under 24 hours increased from 73.9% in PRE to 87.3% in POST [RR = 1.2 (CI95% = 0.97-1.43). We identified 35 patients with ME, 9.7% of them in PRE and 8.1% in POST (RR = 0.84 (CI95% = 0.44-1.58)]. The degree of acceptance of the pharmacist recommendation increased from 53.3% in PRE to 68.3% in POST [RR = 1.3 (CI95% = 1.02- 1.62)]. CONCLUSIONS: The inclusion of the Therapeutic Drug Monitoring Report (TDMR) in the Electronic Clinical Record increases the degree of acceptance of recommendations, and may reduce the delay in treatment modifications, reducing MEs and improving the process quality in terms of efficacy and safety.

Objetivos: Valorar la integración del informe de monitorización farmacocinética (IMFC) en la historia clínica electrónica (HCE). Método: Estudio observacional ambispectivo de cohortes de 149 días de duración: PRE (retrospectiva, 49 días) con emisión del IMFC en papel y POST (prospectiva, 100 días) con emisión del IMFC integrado en HCE. Criterios de exclusión: Pacientes no ingresados, solicitudes de monitorización farmacocinética de unidades de críticos y neonatos, así como monitorizaciones cuyo objetivo no era el ajuste posológico. VARIABLES: Número de IMFC elaborados, número de pacientes ingresados con IMFC, tiempo de demora de las adecuaciones del tratamiento definidas como número de adecuaciones realizadas en el tratamiento en más o en menos 24 horas respecto al momento de emisión del IMFC, y errores de medicación (EM) asociados a dicha demora, así como grado de aceptación del IMFC. Resultados: Se realizaron 690 IFC en 391 pacientes, 339 en PRE (n = 206) y 351 en POST (n = 185). El número de modificaciones realizadas en menos de 24 horas aumentó del 73,9% en PRE al 87,3% en POST [RR = 1,2 (IC95% = 0,97-1,43)]. Se identificaron 35 pacientes con EM, siendo 9,7% en PRE y 8,1% en POST [RR = 0,84 (IC95% = 0,44-1,58)]. El grado de aceptación de la recomendación farmacéutica se incrementó de 53,3% en PRE a 68,3% en POST [RR = 1,3 (IC95% = 1,02-1,62)]. Conclusiones: La integración del informe de monitorización farmacocinética en la historia clínica electrónica incrementa el gra do de aceptación de las recomendaciones y puede disminuir la demora de las adecuaciones del tratamiento reduciendo los EM, mejorando con ello la calidad del proceso en eficacia y seguridad.

Cellular Uptake of Glucocerebrosidase in Gaucher Patients Receiving Enzyme Replacement Treatment.

BACKGROUND: Enzyme replacement therapy (ERT) is currently the standard treatment for patients with Gaucher disease type I (GD1), but the pharmacokinetics have hardly been studied. This study aimed to quantify in vivo enzyme activity in peripheral leukocytes from patients receiving long-term treatment with imiglucerase or velaglucerase for GD1, and set out to assess the process of enzymatic uptake by peripheral leukocytes. METHODS: A prospective semi-experimental study was conducted. Four time points for blood withdrawal were planned per patient to quantify the intra-leukocyte enzymatic activity. In order to assess the uptake process, the rate of enzyme uptake by leukocytes (Rupt) and the rate of enzyme disappearance from the plasma (Rdis) were estimated. RESULTS: Eight GD1 patients were included. Intra-leukocyte activity was 24.31 mU/mL [standard deviation (SD) 6.32 mU/mL; coefficient of variation (CV) 25.96 %] at baseline and 27.14 mU/mL (SD  6.96 mU/mL; CV 25.65 %) at 15 min post-perfusion. The relationships with the administered dose were linear. The Rupt value was 37.73 mU/mL/min [95 % confidence interval (CI) 25.63-49.84] and showed a linear correlation with the administered enzyme dose (p < 0.05), and the Rdis value was 189.43 mU/mL/min (95 % CI 80.31-298.55) and also showed a linear correlation with the dose (p < 0.05). CONCLUSION: This was the first in vivo study to quantify the accumulated enzymatic activity in patients receiving ERT for GD1. It showed that intra-leukocyte activity at baseline and at 15 min post-perfusion could be used as a possible marker for therapeutic individualization in patients receiving ERT for GD1.