Ana Luisa Robles Piedras

In developed countries, clinical pharmacists perform various activities depending on the available resources and the health system, and TDM represents one of the fundamental responsibilities, this activity is performed according to the specific pharmacotherapy of the patient, and includes the evolution of the disease, risk factors and treatment goals. In Mexico, the practice of clinical pharmacy, is a relatively new discipline, and there is not yet a specialized service that performs monitoring in which pharmacokinetic concepts are applied. Therefore, it is highly important to promote the integration and participation of hospital clinical pharmacists in the individualization of pharmacological therapies, and to acknowledge the benefits that all this provides.

Introducción: en México, la cuantificación de fármacos en plasma se utiliza para comprobar la toxicidad, el cumplimiento y la titulación de dosis en el tratamiento con fármacos anticonvulsivos como el ácido valproico (AVP), pero sin considerar los principios de farmacocinética debido a la ausencia de farmacéuticos clínicos en el Sistema de Salud. Método: el presente estudio es un análisis retrospectivo que incluye los datos de concentración plasmática de ácido valproico en pacientes pediátricos de 1 a 15 años de edad, con diagnóstico confiable de epilepsia. Resultados: se revisaron los archivos de 260 pacientes, se encontró que solo el 56,5% de los pacientes tenían niveles séricos en estado estacionario. Los niveles plasmáticos de AVP se encontraron a nivel subterapéutico en el 22% de los pacientes y el 15% tenían niveles tóxicos. El análisis muestra que los niños menores de cinco años aparecen como un grupo heterogéneo para las variables estudiadas. Conclusiones: debido a la falta ...

Vancomycin, a glycopeptide antibiotic, was developed-and released in the 1950's for the treatment of aerobic gram-positive infections and has been widely used mainly in the treatment of methicillin-resistant Staphylococcus aureus infections. Early reports regarding the possibility of nephrotoxicity and ototoxicity led to concern about the use of vancomycin and the need to monitor serum concentrations. In Mexico, the National Institute of Cardiology measures serum level of some drugs, such as vancomycin on a routine basis. Nevertheless, although a large number of measurements are made, the quantification of drug in serum is only used by physicians as a empiric parameter for dose adjustment. The aim of this work was to know whether dosing was appropriate taking the therapeutic interval as a commonly accepted baseline and to propose viable alternatives in the case dosing was inadequate. Peak and through vancomycin levels were analyzed retrospectively (n=295), in patients from 18 to...

Tacrolimus, a macrolide immunosuppressant agent, is indicated for the prophylaxis of organ rejection in patients receiving allogenic liver or kidney transplantation. Successful therapy is complicated by both intra- and inter-patient variability in drug absorption, coupled with the drug's narrow therapeutic index. Moreover, clearance, is significantly affected by co-administration with food and with additional factors such as length of posttransplantation time. At the National Institute of Cardiology, Mexico, the measure of tacrolimus levels is carried out as a common analysis on patients who have been transplanted as a measure to make empiric doseage adjustments. The purpose of this study was to investigate whether tacrolimus levels exceed the desired therapeutic range in adult patients being initiated on a dosage regimen and to establish the use of pharmacokinetic concepts to avoid organ rejection and other complications related to tacrolimus over-exposure. The patients were fo...

The pharmacokinetics of the immunosuppressive drugs is complex and unpredictable. A narrow therapeutic index unique to each patient, as well as variable absorption, distribution, and elimination, are characteristics of these drugs. Therapeutic drug monitoring plays a key role in helping clinicians maintain blood and plasma levels of immunosuppressive drugs within their respective therapeutic ranges. Variation in concentrations outside the narrow therapeutic ranges can result in adverse clinical outcomes. Therapeutic drug monitoring ensures that concentrations are not too high or too low, thereby reducing the risks of toxicity or rejection, respectively. This chapter reviews the general principles of therapeutic drug monitoring of the immunosuppressive drugs: cyclosporine, tacrolimus, mycophenolic acid, sirolimus and everolimus. INTRODUCTION The first successful kidney transplantation was performed in the mid-1950s and marked the advent of a new effective therapy for end-stage renal ...

La farmacocinética se puede definir como la “relación entre la dosis administrada y la concentración plasmática de un fármaco”, y esto implica el estudio de los diferentes procesos de absorción, distribución, metabolismo y excreción. Las modificaciones en la farmacocinética ayudan a explicar las diferentes respuestas que se presentan entre diferentes sujetos, dándose así la variabilidad interindividual, a su vez, la aproximación farmacocinética para definir la variabilidad interindividual en la respuesta a los fármacos necesita obligatoriamente de una explicación genética para entender dicho concepto. La farmacogenética estudia las causas genéticas de las variaciones individuales del ADN en la respuesta a los fármacos, y la farmacogenómica, analiza todo el genoma (nivel de ADN, ARN) de los determinantes genéticos de la eficacia y toxicidad de los fármacos.

Vancomycin, a glycopeptide antibiotic, was developed-and released in the 1950's for the treatment of aerobic gram-positive infections and has been widely used mainly in the treatment of methicillin-resistant Staphylococcus aureus infections. Early reports regarding the possibility of nephrotoxicity and ototoxicity led to concern about the use of vancomycin and the need to monitor serum concentrations. In Mexico, the National Institute of Cardiology measures serum level of some drugs, such as vancomycin on a routine basis. Nevertheless, although a large number of measurements are made, the quantification of drug in serum is only used by physicians as a empiric parameter for dose adjustment. The aim of this work was to know whether dosing was appropriate taking the therapeutic interval as a commonly accepted baseline and to propose viable alternatives in the case dosing was inadequate. Peak and through vancomycin levels were analyzed retrospectively (n=295), in patients from 18 to...

To develop explicit, reliable appropriateness criteria for antiepileptic drug level monitoring and to assess the appropriateness of monitoring in one tertiary care institution. Appropriateness criteria derived from the literature and through expert opinion were used to evaluate a stratified random sample of antiepileptic drug level determinations obtained from chart review. Tertiary care center performing more than 10,000 antiepileptic drug level determinations per year. A total of 330 inpatients in whom antiepileptic drug levels were measured a total of 855 times. Drug levels were assessed at least 200 times for each of four antiepileptic drugs (phenytoin, carbamazepine, phenobarbital, and valproic acid). The proportion of antiepileptic drug levels with an appropriate indication and, of those, the proportion sampled appropriately. Overall, 27% (95% confidence interval, 24% to 30%) of levels had an appropriate indication. Interrater agreement for appropriateness was substantial (kappa = 0.61). There was no significant difference in the appropriateness rate among the four drugs (range, 25% to 29%). Of the 624 antiepileptic drug level determinations considered inappropriate (73%), only four (0.6%) were more than 20% higher than the upper limit of normal, and none of the four patients had clinical signs of drug toxicity. A median of six levels (range, one through 69) was determined per patient, and the median interval between level determinations was 24 hours. Of the 27% of level determinations with an appropriate indication, 51% were sampled correctly, resulting in an overall appropriateness rate of 14%. Only 27% of antiepileptic drug level determinations had an appropriate indication, and half of these were not sampled correctly. Routine daily monitoring without pharmacological justification accounted for most of the inappropriate drug level determinations. Efforts to decrease inappropriate monitoring may result in substantial cost reductions without missing important clinical results.

Tacrolimus, a macrolide immunosuppressant agent, is indicated for the prophylaxis of organ rejection in patients receiving allogenic liver or kidney transplantation. Successful therapy is complicated by both intra- and inter-patient variability in drug absorption, coupled with the drug's narrow therapeutic index. Moreover, clearance, is significantly affected by co-administration with food and with additional factors such as length of posttransplantation time. At the National Institute of Cardiology, Mexico, the measure of tacrolimus levels is carried out as a common analysis on patients who have been transplanted as a measure to make empiric doseage adjustments. The purpose of this study was to investigate whether tacrolimus levels exceed the desired therapeutic range in adult patients being initiated on a dosage regimen and to establish the use of pharmacokinetic concepts to avoid organ rejection and other complications related to tacrolimus over-exposure. The patients were fo...

En este siglo XXI, el uso de los medicamentos se ha convertido en una de las medidas terapéuticas más importantes para restablecer, mantener la salud e incrementar la esperanza de vida de la población. Sin embargo, para garantizar una terapia eficaz y sin efectos secundarios, es fundamental conocer con precisión tanto al fármaco, como en la forma en que se administra. Debido a que es muy frecuente que en los pacientes se tenga una ingesta simultánea de varios medicamentos y principalmente, a que si se están administrando esos medicamentos es porque está presente un estado de enfermedad, las alteraciones funcionales de varios órganos del cuerpo y las posibles interacciones entre los fármacos, pueden dar lugar al surgimiento de situaciones complejas, cuyas consecuencias no se pueden predecir adecuadamente sin el conocimiento de la farmacocinética de los fármacos.

El Monitoreo Terapéutico de Fármacos (TDM) es una herramienta que puede guiar al médico para proporcionar una terapia farmacológica efectiva y segura a un paciente de manera individualizada. Es una herramienta de trabajo en equipo. El farmacéutico clínico desempeña un papel importante para guiar al equipo conformado por médicos, enfermeras y profesionales de laboratorio. El TDM implica no solo medir las concentraciones del fármaco, sino también la interpretación clínica del resultado. Esto requiere conocimiento de la farmacocinética, tiempo de muestreo, historial de medicación, el estado clínico del paciente y los resultados de laboratorio específicos.

La farmacocinética es el estudio de la evolución temporal de las concentraciones de un fármaco y/o metabolitos en un organismo (fluidos, tejidos, compartimentos extracorporales) y de las relaciones matemáticas que permitan interpretar los datos a través de modelos definidos. Es el estudio del proceso ADME (absorción, distribución, metabolismo y excreción) que sufre un fármaco una vez administrado a un individuo. Asimismo, la farmacocinética constituye un aspecto importante de la terapia con medicamentos y del diagnóstico de la función de los órganos. Si se realizara una estimación de los cambios que influyen en la terapia, con los fármacos que poseen un amplio rango terapéutico, se observaría que es muy probable que éstos causarán ningún daño; sin embargo, para fármacos con un margen terapéutico estrecho, se recomienda llevar a cabo un control, a través de la medición de concentraciones y posiblemente, la corrección del régimen de terapia, particularmente si se producen efectos secu...

Tacrolimus, a macrolide immunosuppressant agent, is indicated for the prophylaxis of organ rejection in patients receiving allogenic liver or kidney transplantation. Successful therapy is complicated by both intra- and inter-patient variability in drug absorption, coupled with the drug's narrow therapeutic index. Moreover, clearance, is significantly affected by co-administration with food and with additional factors such as length of posttransplantation time. At the National Institute of Cardiology, Mexico, the measure of tacrolimus levels is carried out as a common analysis on patients who have been transplanted as a measure to make empiric doseage adjustments. The purpose of this study was to investigate whether tacrolimus levels exceed the desired therapeutic range in adult patients being initiated on a dosage regimen and to establish the use of pharmacokinetic concepts to avoid organ rejection and other complications related to tacrolimus over-exposure. The patients were fo...

Vancomycin, a glycopeptide antibiotic, was developed-and released in the 1950's for the treatment of aerobic gram-positive infections and has been widely used mainly in the treatment of methicillin-resistant Staphylococcus aureus infections. Early reports regarding the possibility of nephrotoxicity and ototoxicity led to concern about the use of vancomycin and the need to monitor serum concentrations. In Mexico, the National Institute of Cardiology measures serum level of some drugs, such as vancomycin on a routine basis. Nevertheless, although a large number of measurements are made, the quantification of drug in serum is only used by physicians as a empiric parameter for dose adjustment. The aim of this work was to know whether dosing was appropriate taking the therapeutic interval as a commonly accepted baseline and to propose viable alternatives in the case dosing was inadequate. Peak and through vancomycin levels were analyzed retrospectively (n=295), in patients from 18 to 65 yr old with diagnosis of sepsis. The relationship between administered dose and measured blood levels was established. The equation that characterizes the study population was obtained based on a single compartment model considering the proportional relationship between vancomycin and creatinine clearance. The analysis shows that only 44% of C(trough) and 47% of C(peak) values represented therapeutic levels, with the remainder either toxic or ineffective.