Katherine M Langan1, Jovan Jacob2, Jian Li2, Roger L Nation2, Rinaldo Bellomo3, Benjamin Howden4, Paul D R Johnson4. 1. Department of Infectious Diseases, Austin Health, Melbourne, VIC, Australia. rinaldo.bellomo@austin.org.au. 2. Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia. 3. Department of Medicine, University of Melbourne, Melbourne, VIC, Australia. 4. Department of Infectious Diseases, Austin Health, Melbourne, VIC, Australia.
Abstract
OBJECTIVE: To test whether a prolonged 3-hour infusion of meropenem 500mg achieves an equivalent proportion of time above the minimal inhibitory concentration (MIC) (%TMIC) to that of meropenem 1000mg given over 30 minutes. DESIGN, SETTING AND PARTICIPANTS: A randomised crossover study in 10 critically ill patients. METHOD: We administered meropenem as a 1000mg, 30-minute infusion or as a 500mg, 3-hour infusion. We determined serial plasma concentrations for each dosing episode and performed comparisons of %TMIC at different MICs. OUTCOME MEASURES: The percentage of time that meropenem was above its MIC. RESULTS: For low MICs (≤2 mg/L), both regimens attained a %TMIC >40% in all patients. For an MIC of 4mg/L, this target was attained in all but one patient, but with an MIC of 8mg/L, three patients in each group had a %TMIC <40%. There was no difference in target attainment between the two regimens for MICs up to 8mg/L. There was marked variability in the pharmacokinetic and hence the pharmacokinetic-pharmacodynamic parameters between individuals. Several patients had elevated creatinine clearances and, with both regimens, their target attainment was poor. CONCLUSIONS:Meropenem at 1000mg over 30 minutes achieved a similar %TMIC to meropenem at 500mg given over 3 hours. Meropenem pharmacokinetics were highly variable from individual to individual.
RCT Entities:
OBJECTIVE: To test whether a prolonged 3-hour infusion of meropenem 500mg achieves an equivalent proportion of time above the minimal inhibitory concentration (MIC) (%TMIC) to that of meropenem 1000mg given over 30 minutes. DESIGN, SETTING AND PARTICIPANTS: A randomised crossover study in 10 critically illpatients. METHOD: We administered meropenem as a 1000mg, 30-minute infusion or as a 500mg, 3-hour infusion. We determined serial plasma concentrations for each dosing episode and performed comparisons of %TMIC at different MICs. OUTCOME MEASURES: The percentage of time that meropenem was above its MIC. RESULTS: For low MICs (≤2 mg/L), both regimens attained a %TMIC >40% in all patients. For an MIC of 4mg/L, this target was attained in all but one patient, but with an MIC of 8mg/L, three patients in each group had a %TMIC <40%. There was no difference in target attainment between the two regimens for MICs up to 8mg/L. There was marked variability in the pharmacokinetic and hence the pharmacokinetic-pharmacodynamic parameters between individuals. Several patients had elevated creatinine clearances and, with both regimens, their target attainment was poor. CONCLUSIONS:Meropenem at 1000mg over 30 minutes achieved a similar %TMIC to meropenem at 500mg given over 3 hours. Meropenem pharmacokinetics were highly variable from individual to individual.
Authors: Dagan O Lonsdale; Emma H Baker; Karin Kipper; Charlotte Barker; Barbara Philips; Andrew Rhodes; Mike Sharland; Joseph F Standing Journal: Br J Clin Pharmacol Date: 2018-11-26 Impact factor: 4.335