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.

Batch and flow injection potentiometric monitoring of ceftriaxone sodium in pharmaceutical reparations using two novel membrane sensors

Two novel potentiometric sensors are prepared, characterized and successfully used for static and continuous determination of ceftriaxone sodium [CRXN]. Both sensors are based on the use of plasticized PVC matrix membranes incorporating tetradodecylmethyl ammonium bromide [TDMAB], ortridodecylmethyl ammonium chloride [TDMAC] ion-exchangers and used for quantitative determination of CRXN at concentration level down to 29 micro M using both sensors with a good accuracy. Both sensors offer the advantages of fast response, reasonable selectivity, elimination of drug pre-treatment or separation steps, low cost and possible interfacings with computerized and automated systems. The use of plasticized membrane electrodes were used for continuous monitoring of CRXN offers the advantages of simple design, ease of construction and possible applications to small volumes of drug solutions with little manipulation and without pre-treatment. Both detectors display a wide dynamic measurement range of the drug under continuous mode of operation with a flow rate of 2.0 ml.min[-1] and used for quantitative determination of CRXN. The developed sensors were utilized in static continuous modes successfully for the determination of CRXN in pure powders and in dosage forms. It is worth noting that the developed membrane electrodes exhibited good selectivity toward CRXN over other cephalosporins such as; cefradine, ceftazidime, cefadroxil, cefaclor and cefoperazone, as well as other additives found in the pharmaceutical preparations such as; glucose, fructose and maltose

Seguimiento farmacoterapéutico como herramienta para la detección y evaluación de interacciones farmacológicas de medicamentos prescritos a pacientes críticos / Pharmacotherapeutic monitoring as an indispensable tools to anticipate of negative pharmacological interactions in critically ill patients

En la actualidad el seguimiento farmacoterapéutico constituye una de las herramientas imprescindibles para prevenir, detectar y solucionar problemas derivados de la medicación. Dentro de éstos se encuentran las interacciones farmacológicas. Uno de los grupos de pacientes que más preocupación demanda, son los internados en unidades de cuidados intensivos, que debido a su polifarmacia, características fisiológicas y patológicas están más expuestos a presentarlas. Pacientes y métodos: Este estudio evaluó las interacciones farmacológicas reales negativas de pacientes hospitalizados en la Unidad de Cuidados Intensivos de Adulto del Hospital Dr. Gustavo Fricke. Resultados: Se analizaron 128 pacientes, de los cuales 38,3 por ciento presentó al menos una de estas interacciones farmacológicas, siendo su desarrollo influenciado por la estadía hospitalaria y el número de medicamentos administrados. Las asociaciones más frecuentes involucradas fueron furosemida/hidrocortisona, noradrenalina/dopamina e insulina/hidrocortisona generando cuadros de hipokalemia, taquicardia e hiperglicemia, respectivamente. Conclusiones: La monitorización y evaluación de interacciones farmacológicas es necesaria para mejorar la seguridad de la farmacoterapia en los pacientes críticos, especialmente en aquellos con estadía hospitalaria mayor de 10 días y con un promedio de administración diaria de 6 o más fármacos.

Pharmacotherapeutic monitoring, nowadays, constitutes one of the indispensable tools to anticipate, detect and solve problems derived from medication. Among these problems, pharmacological interactions can be found. People hospitalized on intensive care units are the most care demanding patient group; due to their polypharmacy, physiological and pathological characteristics they are more likely to be presented. Patients and methods: This research evaluated actual negative pharmacological interactions of the patients that are hospitalized in the adult intensive care units of the hospital Dr. Gustavo Fricke. Results: 128 patients were analyzed, of which 38.3 percent presented at least one of these interactions and their development was being influenced by their stay in the hospital and the number of administered medication. The associated medications mainly involved were furosemide/hydrocortisone, noradrenaline/ dopamine and insulin/hydrocortisone, which produced hypokalemia, tachycardia and hyperglycemia conditions respectively. Conclusions: Monitoring and evaluation of drug interactions is needs to improve the safety of pharmacotherapy in critically ill patients, especially those with hospital stay longer than 10 days and an average of daily administration of 6 or more drugs.

Prevalence of potential drug interactions in patients in an intensive care unit of a university hospital in Brazil

OBJECTIVES: To investigate the prevalence of potential drug interactions at the intensive care unit of a university hospital in Brazil and to analyze their clinical significance. METHODS: This cross-sectional retrospective study included 299 patients who had been hospitalized in the intensive care unit of the hospital. The drugs administered during the first 24 hours of hospitalization, in the 50th length-ofstay percentile and at the time of discharge were analyzed to identify potential drug-drug and drug-enteral nutrition interactions using DRUG-REAXH software. The drugs were classified according to the anatomical therapeutic chemical classification. RESULTS: The median number of medications per patient was smaller at the time of discharge than in the 50th length-of-stay percentile and in the first 24 hours of hospitalization. There was a 70 percent prevalence of potential drug interactions at the intensive care unit at the studied time points of hospitalization. Most of the drug interactions were either severe or moderate, and the scientific evidence for the interactions was, in general, either good or excellent. Pharmacodynamic interactions presented a subtle predominance in relation to pharmacokinetic interactions. The occurrence of potential drug interactions was associated with the number of medications administered and the length of stay. Medications that induced cytochrome P450, drugs that prolong the QT interval and cardiovascular drugs were pharmacotherapy factors associated with potential drug interactions. CONCLUSION: The study showed that potential drug interactions were prevalent in the intensive care unit due to the complexity of the pharmacotherapies administered. The interactions were associated with the number of drugs, the length of stay and the characteristics of the administered medications.

Antiepileptic TDM pattern at a tertiary care hospital in India.

Therapeutic drug monitoring, a comparatively new investigational procedure in clinical pharmacology, is considered very beneficial to epilepsy patients though it increase the health care cost. Aim of this study was to determine the pattern of use of antiepileptic drug level monitoring over the last 7 years in our tertiary care centre and to critically comment on its utility. Retrospective data audit of archived data from 1998 to 2004 and age, sex, estimated levels of phenytoin, carbamazepine and phenobarbitone by HPLC were noted down, tabulated and compared. Chi square test was used for analysis. Three thousand five jundred thirty four blood samples of patients requesting for 4213 estimations of phenytoin, phenobarbitone or carbamazepine were received. Among the obtained samples, 44.0% (1058) were of children, 68.0% (2402) were of males, 0.6% (22) patients were getting 3 and 18.0% (635) getting 2, antiepileptic medications. 13.0% (546) samples showed level in the toxic range and 39.0% (1653) in lower range. There was increasing demand observed for estimation of antiepileptic drugs, over the 7 years. The number of abnormal values of phenytoin, phenobarbitone and carbamazepine did not show any significant difference over the years. The pattern was similar to that observed in other countries.

Vigabatrin and Visual Field Defects in Pediatric Epilepsy Patients

We studied the prevalence, type and severity of vigabatrin (VGB)-attributed visual field defects (VFDs), and used these data to assess the associated risk factors in pediatric patients. Medical records were retrospectively reviewed for 67 pediatric patients who received VGB alone or in combination with other antiepileptic drugs, and who had undergone visual field examinations using a Humphrey visual field analyzer. Of the 67 patients, 15 had VGB-attributed VFDs: 13 had nasal arcuate type, 1 had nasal and temporal constricted type and 1 had nasal constricted type. In terms of severity, 7 patients had Grade I VGB-attributed VFDs, 5 had Grade II, 2 had Grade III, and 1 had Grade IV. Although there were no significant differences between the VFD and non-VFD groups with regards to all tested parameters, there were no cases of VGB-attributed VFDs in patients with total treatment durations <2 yr and cumulative doses <10 g/kg. In conclusion, the prevalence of VGB-attributed VFDs in VGB-treated pediatric epilepsy patients was 22%. The high frequency of VGB-attributed VFDs indicates that physicians should inform all patients of this risk prior to VGB treatment and perform periodic visual field examinations.

Monitoreo terapéutico del litio

El litio es un fármaco de elección para el tratamiento de la manía y para el mantenimiento a largo plazo en la prevención de las crisis maníacas o depresivas del trastorno bipolar. Un conocimiento profundo del litio es necesario para alcanzar una utilización más segura y efectiva. Es un fármaco que debe ser utilizado con mucha precaución debido a su estrecha ventana terapéutica y la letalidad de la toxicidad relacionada con el mismo. Los pacientes deben ser evaluados clínica y paraclínicamente antes de iniciar la terapia con litio. Las interacciones farmacológicas deben ser tenidas presentes y se recomienda que la litemia, función tiroidea y función renal deben ser evaluadas mediante el laboratorio en asocio con un seguimiento clínico estricto. Las muestras de sangre para efectuar el monitoreo deben ser tomadas luego de cuatro días de estar tomando una dosis constante, doce horas después de la dosis de la noche y justo antes de tomar la de la mañana.

Monitoreo terapéutico de drogas

La formulación racional requiere un conocimiento adecuado de la patología del paciente y de las propiedades farmacocinéticas y farmacodinámicas del medicamento seleccionado. El clínico debe elegir un esquema de dosis que alcance una concentración óptima en el órgano enfermo, la cual no debe ser demasiado baja ni demasiado alta; en el primer caso, no se logrará el objetivo terapéutico, mientras que en el segundo, los efectos adversos o tóxicos serán molestos o intolerables para el paciente. La finalidad del monitoreo terapéutico de drogas es darle al clínico la información que le permita individualizar el tratamiento para cada uno de sus pacientes. Este módulo evalúa la utilidad del monitoreo terapéutico de drogas para ciertos medicamentos en el manejo individual de los pacientes.