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

Abstract

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 C max, t max, and AUC 0-24 h determined using the trapezoidal method, were obtained for a Markov simulation that would allow for determining the likelihood of achieving a AUC 0-24 h /MIC ratio above 70 for infections caused by susceptible B. fragilis. Results: C max (24,03 ± 6,89 mg/L) and t max (1,20 ± 0.80 hrs) and the value of AUC 0-24 h (241.91 ± 48.14 mg * h/L) were determined. The probability of obtaining a AUC 0-24 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 AUC 0-24 h /MIC ratio above 70 for the treatment of anaerobic infections.