Prediction of the Impact of CYP2C19 Polymorphism on Drug-Drug Interaction between Voriconazole and Tacrolimus Using Physiologically-Based Pharmacokinetic Modelling

Abstract Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole.

Measuring life skills of adolescents in a secondary school of Kathmandu: an experience.

OBJECTIVE: The objective of this study was to develop a scale to measure life skills and to assess the levels of life skills in adolescents of a secondary school at Kathmandu. METHODOLOGY: A descriptive, cross sectional survey of adolescents from class VIII, IX, and X of a public co-educational secondary school of Kathmandu was done with the help of self-administered questionnaires prepared in English and translated into Nepali. Focus Group Discussions consisting of boys only, girls only and a mixed group comprising of one student from each section of each class were conducted to confirm the results of the study. All the data obtained from the questionnaire survey were edited, coded and entered into EPI info Version 6. RESULTS: A total of 347 adolescents participating in the study. 176 adolescents (51%) had life skill scores above the mean, and was termed as having "high level" of life skills and 171 (49%), had "low level" of life skills scores. Mother's education was significantly associated with increased level of life skills in adolescents P=.001). CONCLUSIONS: Most of the teachers were not aware of the concept of life skills. Maternal education was significantly associated with higher life skill levels in adolescents. Connectedness and family support were other important factors influencing the level of life skills in the adolescents.

Actitud del niño con asma frente al síntoma en institucione públicas y privadas / The attitude of a child with asthma towards sympton in public and private institutions

La actitud del niño ante la enfermedad se puede dividir en: sobreadaptados (con características de orden y prolijidad, buen rendimiento intelectual y sin dificultades aparentes de perentectomía, con reacción asmática tardía y respecto del conflicto, de alto riesgo en adolescencia), y actuadores (dramatiza su enfermedad, dependencia manifiesta con sus padres generando alto monto de ansiedad familiar, reacción asmática inmediata al conflicto, con pronóstico más favorable). Se comprobará si existe una diferencia significativa según esta clasificación en pacientes del ámbito privado y público. Se estudiaron 60 niños provenientes de un centro de atención privado, y 60 niños de una institución pública, con diagnóstico de asma y edades entre 4-12 años. Se aplicó: Entrevista operativa semi-abierta y entrevista pautada con ambos padres; Tests: Santuchi-Bender, Casa pintada, Figura humana, Familia, Desiderativo, Cat, Nemi y Raven. De acuerdo a la clasificación utilizada se encontraron: ámbito privado: 32 sobreadaptados (53 por ciento) y 28 actuadores (47 por ciento); ámbito público: 38 sobreadaptados (63 por ciento, p=NS) y 22 actuadores (37 por ciento, p=NS). Esto nos plantea la necesidad de un abordaje interdisciplinario para la detección temprana de los rasgos de sobreadaptación, dado que en este tipo de pacientes encontramos la paradoja de que lo ideal esconde lo mortífero: cuando aparece el pasaje al acto puede ser tarde