Steady-state pharmacokinetics and pharmacodynamics of meropenem in hospitalized patients.
OBJECTIVE
To evaluate the steady-state pharmacokinetics and pharmacodynamics of meropenem 500 mg every 6, 8, and 12 hours, based on renal function, in hospitalized patients.


METHODS
Prospective, open-label, steady-state pharmacokinetic study.


METHODS
One tertiary care medical center and one community hospital.


METHODS
Twenty adult patients (12 men, 8 women) with suspected or documented bacterial infections requiring antimicrobial therapy.


METHODS
Patients received 30-minute infusions of meropenem 500 mg every 6 hours (group 1), every 8 hours (group 2), or every 12 hours (group 3) based on estimated creatinine clearances greater than 60, 40-60, or 10-39 ml/minute, respectively.


RESULTS
Serial blood samples were collected after 2 or more days of therapy. Meropenem concentrations were determined by high-performance liquid chromatography, and pharmacokinetic data were analyzed by noncompartmental methods. Monte Carlo simulations (10,000 patients) were performed to calculate the cumulative fraction of response (CFR) for a percentage of the dosing interval that free drug concentrations remain above the minimum inhibitory concentration (fT>MIC) of 40% by using pharmacokinetic data for each group and MIC data for seven gram-negative pathogens from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC, 2004-2005) database. Maximum and minimum serum concentrations (mean +/- SD) were 29.2+/-9.8 and 2.4+/-1.1 microg/ml, 33.2+/-8.5 and 3.8+/-2.7 microg/ml, and 33.5+/-4.7 and 4.9+/-1.6 microg/ml for groups 1, 2, and 3, respectively. The half-life values were 2.5+/-0.9, 3.4+/-1.3, and 6.1+/-1.4 hours, and the values for volume of distribution at steady state were 29.3+/-8.7, 23.8+/-8.1, and 28.7+/-8.6 L for groups 1, 2, and 3, respectively. For all three groups, the CFR was greater than 90% for the enteric pathogens and Pseudomonas aeruginosa and 82.4-85.2% for Acinetobacter species.


CONCLUSIONS
Pharmacodynamic analyses suggest that regimens of meropenem 500 mg every 6, 8, or 12 hours, adjusted for renal function, are acceptable for treatment of infections caused by enteric gram-negative pathogens and P. aeruginosa. However, more aggressive dosing or alternative dosing strategies may be necessary for Acinetobacter species.
Cheatham
S Christian
SC
Department of Pharmacy, St. Francis Hospital, Beech Grove, Indiana, USA.
Kays
Michael B
MB
Smith
David W
DW
Wack
Matthew F
MF
Sowinski
Kevin M
KM
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies; D013845:Thienamycins / Q000493:pharmacokinetics* / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem