Pharmacokinetics of imipenem in healthy volunteers following administration by 2 h or 0.5 h infusion

Objectives: The aim of this study was to demonstrate the t > MIC of 0.5 and 1 g of imipenem when administered by 2 h infusion every 6 h compared with 0.5 g of imipenem when administered by 0.5 h infusion every 6 h. Methods: The study was a randomized three-way crossover study with a 30 h wash-out period in eight healthy volunteers. Each subject received imipenem in three regimens: (i) a 0.5 h infusion of 0.5 g every 6 h for three doses; (ii) a 2 h infusion of 0.5 g every 6 h for three doses; and (iii) a 2 h infusion of 1 g every 6 h for three doses. Results: Following 0.5 h infusion of 0.5 g, the percentages of time above four times an MIC of 4, 2 and 1 mg/L were 21.5 +/- 2.2%, 38.6 +/- 3.5% and 57.5 +/- 4% of a 6 h interval, respectively. For the 2 h infusion of 0.5 g, the percentages of time above four times an MIC of 4, 2 and 1 mg/L were 26.9 +/- 8.5%, 48.0 +/- 3.5% and 65.4 +/- 3.2% of a 6 h interval, respectively. For the 2 h infusion of 1 g, the percentages of time above four times an MIC of 4, 2 and 1 mg/L were 51.6 +/- 5.4%, 67.8 +/- 4.5% and 87.8 +/- 5.6% of a 6 h interval, respectively. Conclusions: A 2 h infusion resulted in a greater t > MIC than those after a 0.5 h infusion and intermittent infusion may be a useful mode of administration of imipenem in tropical countries.