Pharmacokinetics of meropenem in critically ill patients receiving continuous venovenous haemofiltration: A randomized controlled trial of continuous infusion versus intermittent bolus administration

Jamal, Janattul-Ain and Mat Nor, Mohd Basri and Mohamad Nor, Fariz Safhan and Udy, Andrew A and Wallis, Steven C and Lipman, Jeffrey and Roberts, Jason A. (2015) Pharmacokinetics of meropenem in critically ill patients receiving continuous venovenous haemofiltration: A randomized controlled trial of continuous infusion versus intermittent bolus administration. International Journal of Antimicrobial Agents , 45 (1). pp. 41-45. ISSN 0924-8579

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Abstract

The objective of this study was to describe the pharmacokinetics of meropenem, administered by continuous infusion (CI) or intermittent bolus (IB), in critically ill patients receiving continuous venovenous haemofiltration (CVVH) and to evaluate the frequency of pharmacokinetic/pharmacodynamic target attainment with each dosing strategy. This was a prospective, randomised controlled trial in critically ill patients receiving CVVH and administered meropenem by CI or IB. Serial meropenem concentrations in plasma and ultrafiltrate were measured after administration of a standard total daily dose (4 g/day on Day 1, followed by 3 g/day thereafter) on two occasions during antibiotic therapy. Meropenem pharmacokinetic parameters were calculated using a non-compartmental approach. Sixteen critically ill patients receiving CVVH concurrently treated with meropenem were randomised to CI (n=8) orIB dosing (n= 8). IB administration resulted in higher maximum concentrations (Cmax) [64.7 (58.9–80.3)and 64.8 (48.5–81.8) mg/L, respectively] on both sampling occasions compared with CI (P< 0.01 and P= 0.04, respectively). CI resulted in a higher meropenem steady-state concentration (Css) on occasion 1 [26.0 (24.5–41.6) mg/L] compared with the minimum concentration (Cmin) observed for IB patients [17.0(15.7–19.8) mg/L;P< 0.01]. CVVH contributed to ca. 50% of meropenem total clearance in these patients. The administered meropenem doses resulted in plasma drug concentrations that were >4×the targeted susceptibility breakpoint (2 mg/L) for 100% of the dosing interval, for both groups, on both occasions. CI could be an alternative to IB for meropenem administration in critically ill patients receiving CVVH.

Item Type:	Article (Journal)
Additional Information:	5608/40454
Uncontrolled Keywords:	Meropenem Continuous infusion CVVH Intensive care
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Medicine > Department of Anaesthesiology & Intensive Care
Depositing User:	Dr. Mohd Basri Mat Nor
Date Deposited:	06 Jan 2015 10:03
Last Modified:	06 Apr 2017 16:15
URI:	http://irep.iium.edu.my/id/eprint/40454

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