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

Abstract

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.

Population Pharmacokinetics and Monte Carlo Dosing Simulations of Meropenem during the Early Phase of Severe Sepsis and Septic Shock in Critically Ill Patients in Intensive Care Units

“…As a consequence of these alterations in V and CL, the half-life (t 1/2 ) of antimicrobial agents can be affected, leading to undesirable therapeutic outcomes. In the current study, alterations of the PK of meropenem were found in comparison with an earlier study with healthy volunteers (17). The V of meropenem was greater and the CL of meropenem was lower than the values obtained from the previous study with healthy volunteers (17), resulting in Ͼ2-fold prolongation of the t 1/2 of this agent.…”

“…In the current study, alterations of the PK of meropenem were found in comparison with an earlier study with healthy volunteers (17). The V of meropenem was greater and the CL of meropenem was lower than the values obtained from the previous study with healthy volunteers (17), resulting in Ͼ2-fold prolongation of the t 1/2 of this agent. A possible explanation for the PK changes in this study is that the study was undertaken with seriously ill patients with life-threatening infections and more than one-half of the recruited patients were experiencing renal dysfunction, as defined by MDRD CL Cr values of Յ60 ml/min.…”

Comparison of the Pharmacodynamics of Meropenem in Patients with Ventilator-Associated Pneumonia following Administration by 3-Hour Infusion or Bolus Injection

“…Moreover, the mortality in animals infected with Streptococcus pneumoniae and treated with ␤-lactams is very low when levels of antibiotics exceed the MIC for 40 to 50% of the dosing interval (4). A previous study of healthy volunteers revealed that a 3-h infusion of 1 g of meropenem can maintain serum drug concentrations above the MIC for most pathogens in patients for 60% of an 8-h dosing interval (8). Thus, a 3-h infusion has been proposed as an appropriate mode of administration in tropical countries.…”

“…The maximum plasma concentration (C max ) and the minimum plasma concentration (C min ) were determined by visual inspection of the individual plasma concentration-time profiles. From the individually fitted concentration-time curves, the TϾMICs were calculated for MICs of 16,8,4, and 1 g/ml. Results were expressed as mean values Ϯ standard deviations, and statistical comparisons were made using the Wilcoxon signedrank test.…”

“…The study revealed that a 3-h infusion of either 0.5 or 1 g of meropenem gives greater values for TϾMIC than a 1-g bolus injection. We have therefore suggested that a 3-h infusion every 8 h may be a useful mode of administration in tropical countries (8). For the treatment of most serious infections, including ventilator-associated pneumonia (VAP), this drug should be administered at a dosage of 1 g intravenously every 8 h; if necessary, this dosage can be increased to a maximum of 2 g every 8 h (7).…”