[Pharmacokinetics/pharmacodinamic (PK/PD) evaluation of a short course of oral administration of metronidazole for the management of infections caused by Bacteroides fragilis].

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Morales-Leon F, von Plessing-Rossel C, Villa-Zapata L, Fernandez-Rocca P, Sanhueza-Sanhueza C, Bello-Toledo H, Mella-Montecinos S

[Pharmacokinetics/pharmacodinamic (PK/PD) evaluation of a short course of oral administration of metronidazole for the management of infections caused by Bacteroides fragilis].

Rev Chilena Infectol. 2015 Apr;32(2):135-41. doi: 10.4067/S0716-10182015000300001.

PubMed ID
26065445 [ View in PubMed
]
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 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.

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