Premium
Steady‐State Pharmacokinetics and Pharmacodynamics of Meropenem in Hospitalized Patients
Author(s) -
Cheatham S. Christian,
Kays Michael B.,
Smith David W.,
Wack Matthew F.,
Sowinski Kevin M.
Publication year - 2008
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.28.6.691
Subject(s) - meropenem , pharmacokinetics , medicine , pharmacodynamics , dosing , confidence interval , minimum inhibitory concentration , renal function , pharmacology , anesthesia , antimicrobial , antibiotics , chemistry , antibiotic resistance , biochemistry , organic chemistry
Study 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. Design. Prospective, open‐label, steady‐state pharmacokinetic study. Setting. One tertiary care medical center and one community hospital. Patients. Twenty adult patients (12 men, 8 women) with suspected or documented bacterial infections requiring antimicrobial therapy. Intervention. 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. Measurements and Main 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 ( f T>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 μg/ml, 33.2 ± 8.5 and 3.8 ± 2.7 μg/ml, and 33.5 ± 4.7 and 4.9 ± 1.6 μg/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. Conclusion. 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.