Comparison of the pharmacodynamics of meropenem in healthy volunteers following administration by intermittent infusion or bolus injection

Objectives: The aim of this study was to compare the pharmacokinetics and pharmacodynamics of meropenem when administered by 3 h infusion or bolus injection regimens. Patients and methods: The study was a randomized three-way crossover study with a 1 week wash-out period in 12 healthy volunteers. Each subject received a single dose of meropenem in three regimens: (i) bolus injection of 1 g meropenem; (ii) 3 h infusion of 1 g meropenem; and (iii) 3 h infusion of 0.5 g meropenem. Results: Following bolus injection of 1 g meropenem, the mean+/-s.d. percentages of the t>MIC of 4, 2 and 1 mg/L were 42.50+/-6.20%, 54.38+/-7.64% and 67.04+/-8.47% of an 8 h dosing interval, respectively. For the 3 h infusion of 1 g meropenem, the percentages of the t>MIC of 4, 2 and 1 mg/L were 59.27+/-7.34%, 71.97+/-8.63% and 86.07+/-9.41% of an 8 h dosing interval, respectively. For the 3 h infusion of 0.5 g meropenem, the percentages of the t>MIC of 4, 2 and 1 mg/L were 47.27+/-5.34%, 59.36+/-6.60% and 71.44+/-8.45% of an 8 h dosing interval, respectively. Conclusions: We conclude that a 3 h infusion of 0.5 g or 1 g of meropenem both give greater values for t>MIC than a 1 g bolus and that intermittent infusion may be a useful mode of administration in tropical countries where drug instability may prevent the use of continuous infusion.