Principios de estadística Bayesiana y su relación con la farmacocinética aplicada / Principles of Bayesian statistics and its relationship with applied pharmacokinetics

La metodología estadística Bayesiana permite, si se conoce la probabilidad poblacional de que un suceso ocurra, modificar su valor cuando se dispone de nueva información individual. Aunque las metodologías Bayesiana y frecuentista (clásica) tienen idénticos campos de aplicación, la primera se aplica cada vez más en investigación científica y análisis de big data. En la farmacoterapia moderna, la farmacocinética clínica ha sido responsable de la expansión de la monitorización, facilitada por desarrollos técnico-analíticos y matemático-estadísticos. La farmacocinética poblacional ha permitido identificar y cuantificar las características fisiopatológicas y de tratamiento en una población de pacientes determinada, en particular en pediatría y neonatología, y otros grupos vulnerables, explicando la variabilidad farmacocinética interindividual. Asimismo, la estimación Bayesiana resulta importante como herramienta estadística aplicada en programas informáticos de optimización farmacoterapéutica cuando la monitorización farmacológica se basa en la interpretación farmacocinética clínica. Aunque con ventajas y limitaciones, la optimización farmacoterapéutica basada en la estimación Bayesiana es cada vez más usada en la actualidad, siendo el método de referencia. Esto es particularmente conveniente para la práctica clínica de rutina debido al limitado número de muestras requeridas por parte del paciente, y a la flexibilidad en cuanto a los tiempos de muestreo de sangre para cuantificación de fármacos. Así, la aplicación de los principios Bayesianos a la práctica de la farmacocinética clínica resulta en la mejora de la atención farmacoterapéutica.

If one knows the probability of an event occurring in a population, Bayesian statistics allows mo difying its value when there is new individual information available. Although the Bayesian and frequentist (classical) methodologies have identical fields of application, the first one is increasin gly applied in scientific research and big data analysis. In modern pharmacotherapy, clinical phar macokinetics has been used for the expansion of monitoring, facilitated by technical-analytical and mathematical-statistical developments. Population pharmacokinetics has allowed the identification and quantification of pathophysiological and treatment characteristics in a specific patient popu lation, especially in the pediatric and neonatal population and other vulnerable groups, explaining interindividual variability. Likewise, Bayesian estimation is important as a statistical tool applied in pharmacotherapy optimization software when pharmacological monitoring is based on clinical phar macokinetic interpretation. With its advantages and despite its limitations, pharmacotherapeutic op timization based on Bayesian estimation is increasingly used, becoming the reference method today. This characteristic is particularly convenient for routine clinical practice due to the limited number of samples required from the patient and the flexibility it shows regarding blood sampling times for drug quantification. Therefore, the application of Bayesian principles to the practice of clinical phar macokinetics has led to the improvement of pharmacotherapeutic care.

[Principles of Bayesian statistics and its relationship with applied pharmacokinetics]. / Principios de estadística Bayesiana y su relación con la farmacocinética aplicada.

If one knows the probability of an event occurring in a population, Bayesian statistics allows mo difying its value when there is new individual information available. Although the Bayesian and frequentist (classical) methodologies have identical fields of application, the first one is increasin gly applied in scientific research and big data analysis. In modern pharmacotherapy, clinical phar macokinetics has been used for the expansion of monitoring, facilitated by technical-analytical and mathematical-statistical developments. Population pharmacokinetics has allowed the identification and quantification of pathophysiological and treatment characteristics in a specific patient popu lation, especially in the pediatric and neonatal population and other vulnerable groups, explaining interindividual variability. Likewise, Bayesian estimation is important as a statistical tool applied in pharmacotherapy optimization software when pharmacological monitoring is based on clinical phar macokinetic interpretation. With its advantages and despite its limitations, pharmacotherapeutic op timization based on Bayesian estimation is increasingly used, becoming the reference method today. This characteristic is particularly convenient for routine clinical practice due to the limited number of samples required from the patient and the flexibility it shows regarding blood sampling times for drug quantification. Therefore, the application of Bayesian principles to the practice of clinical phar macokinetics has led to the improvement of pharmacotherapeutic care.

Combinational Effect of CYP3A5 and MDR-1 Polymorphisms on Tacrolimus Pharmacokinetics in Liver Transplant Patients.

OBJECTIVES: Previous studies have reported reduced tacrolimus dose-adjusted exposure in individuals expressing the CYP3A5*1 allele (reference single nucleotide polymorphism identification number 776746). However, results on patients from South America are scarce. The objective of this study was to investigate the influence of CYP3A5 and MDR1 allelic variants and their correlation on the pharmacokinetics of tacrolimus and a modified release formulation of tacrolimus in stable patients with liver transplant. MATERIALS AND METHODS: This was a prospective, single center, open-label study. Included patients were ≥ 18 years old and receiving a stable dose of tacrolimus for at least 6 months. Patients receiving stable treatment of twice daily tacrolimus were switched to a once-daily dose of modified release tacrolimus, on a milligram-to-milligram basis, with the modified release formulation administered for at least 4 weeks. Blood levels of tacrolimus were obtained before and 1 month after treatment was switched to the modified release formulation. RESULTS: The frequency of the intron 3 allelic variant of the CYP3A5 isoform (G-to-A substitution at nucleotide 6986) in recipients was 16.6% and 25% in donors. Dose levels of tacrolimus and the modified formulation were significantly higher in donors and recipients who expressed CYP3A5 versus donors and recipients who did not express this allele. In addition, patients who received a liver from a donor expressing CYP3A5 had significantly lower trough concentrations of tacrolimus and the modified formulation. CYP3A5 expression in the donor liver affected tacrolimus (40.46%, P = .001) and modified formulation (37.56%, P = .001) variability. No association was found between the ABCB1 genotype and levels of tacrolimus or its modified formulation. CONCLUSIONS: Our data suggest that CYP3A5*1 in either the donor or recipient resulted in higher mean daily doses of tacrolimus or its modified formulation to achieve target drug exposure in liver transplant patients.