[Pharmacokinetics/pharmacodinamic (PK/PD) evaluation of a short course of oral administration of metronidazole for the management of infections caused by Bacteroides fragilis]. / Evaluación farmacocinética/farmacodinámica (PK/PD) de un esquema de administración oral de metronidazol en intervalo ampliado para el manejo de infecciones producidas por Bacteroides fragilis.

INTRODUCTION: Metronidazole is the antibiotic of choice for the management of infections caused by anaerobes. Its administration requires multiple daily doses causing increased medication errors. Due to its high post-antibiotic effect and rapid concentration-dependent bactericidal activity, administration of this antibiotic in an extended dosing interval would achieve PK/PD parameters effectively. OBJECTIVE: To assess the probability of achieving effective PK/PD relationship with the administration of 1,000 mg every 24 hours of metronidazole for Bacteroides fragilis infections. METHODS: A clinical trial was conducted in a group of volunteers who received a single oral dose of 500 or 1,000 mg of metronidazole. Determinations of values of Cmax, t max, and AUCC0-24 h. determined using the trapezoidal method, were obtained for a Markov simulation that would allow for determining the likelihood of achieving a AUC0-24 h/MIC ratio above 70 for infections caused by susceptible B. fragilis. RESULTS: Cmax (24,03 ± 6,89 mg/L) and t max (1,20 ± 0.80 hrs) and the value of AUC0-24 h (241.91 ± 48.14 mg * h/L) were determined. The probability of obtaining a AUC0-24 h/MIC ratio greater than 70 was greater than 99%. CONCLUSION: From a pharmacokinetic perspective, with the administration of a daily dose of 1,000 mg of metronidazole, it is possible to achieve a therapeutic goal of AUC0-24 h/MIC ratio above 70 for the treatment of anaerobic infections.

Evaluación farmacocinética/farmacodinámica (PK/PD) de un esquema de administración oral de metronidazol en intervalo ampliado para el manejo de infecciones producidas por Bacteroides fragilis / Pharmacokinetics/pharmacodinamic (PK/PD) evaluation of a short course of oral administration of metronidazole for the management of infections caused by Bacteroides fragilis

Introduction: Metronidazole is the antibiotic of choice for the management of infections caused by anaerobes. Its administration requires multiple daily doses causing increased medication errors. Due to its high post-antibiotic effect and rapid concentration-dependent bactericidal activity, administration of this antibiotic in an extended dosing interval would achieve PK/PD parameters effectively. Objective: To assess the probability of achieving effective PK/PD relationship with the administration of 1,000 mg every 24 hours of metronidazole for Bacteroides fragilis infections. Methods: A clinical trial was conducted in a group of volunteers who received a single oral dose of 500 or 1,000 mg of metronidazole. Determinations of values of Cmax, t max, and AUCC0-24 h. determined using the trapezoidal method, were obtained for a Markov simulation that would allow for determining the likelihood of achieving a AUC0-24 h/MIC ratio above 70 for infections caused by susceptible B. fragilis. Results: Cmax (24,03 ± 6,89 mg/L) and t max (1,20 ± 0.80 hrs) and the value of AUC0-24 h (241.91 ± 48.14 mg * h/L) were determined. The probability of obtaining a AUC0-24 h/MIC ratio greater than 70 was greater than 99%. Conclusion: From a pharmacokinetic perspective, with the administration of a daily dose of 1,000 mg of metronidazole, it is possible to achieve a therapeutic goal of AUC0-24 h/MIC ratio above 70 for the treatment of anaerobic infections.

Introducción: Metronidazol es el antimicrobiano de elección para el manejo de infecciones anaeróbicas. Su administración requiere de dosis múltiples provocando aumento en errores medicamentosos. Debido al efecto post-antibiótico y a la actividad bactericida concentración-dependiente, la administración de metronidazol en intervalos ampliados de administración permitiría alcanzar parámetros PK/PD efectivos. Objetivo: Evaluar la probabilidad de alcanzar una relación PK/PD efectiva con la administración de 1.000 mg cada 24 h de metronidazol para infecciones por Bacteroides fragilis. Método: Se realizó un ensayo clínico sobre un grupo de voluntarios a quienes se les administró una monodosis oral de 500 y 1.000 mg de metronidazol, respectivamente. Se establecieron parámetros farmacocinéticos empleando el método trapezoidal. Se realizó una simulación de Markov que permitiera establecer la probabilidad de alcanzar una relación AUC0-24 h/CIM > 70 en infecciones por B. fragilis. Resultados: Se determinaron los valores de Cmax (24,03 ± 6,89 mg/L), t max (1,20± 0,8h) y AUC0-24 h (241,91 ± 48,14 mg*h/L), con lo cual la probabilidad de alcanzar una relación AUC0-24 h/CIM > 70 con 1.000 mg de metronidazol fue superior a 99%. Conclusión: Con la administración de 1.000 mg cada 24 h sería posible alcanzar una relación PK/PD efectiva para el tratamiento de infecciones anaeróbicas.