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Steady‐state pharmacokinetics and pharmacodynamics of meropenem in morbidly obese patients hospitalized in an intensive care unit
Author(s) -
Cheatham S. Christian,
Fleming Megan R.,
Healy Daniel P.,
Chung Eun Kyoung,
Shea Katherine M.,
Humphrey Melissa L.,
Kays Michael B.
Publication year - 2014
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.196
Subject(s) - meropenem , pharmacodynamics , pharmacokinetics , dosing , medicine , volume of distribution , intensive care unit , anesthesia , body mass index , pharmacology , antibiotics , chemistry , biochemistry , antibiotic resistance
The study objective was to evaluate meropenem pharmacokinetics and pharmacodynamics in morbid obesity. Nine patients hospitalized in an intensive care unit with a body mass index ≥40 kg/m 2 received meropenem 500 mg or 1 g q6h, infused over 0.5 hours. Pharmacokinetic parameters were estimated, and Monte Carlo simulations were performed for 5 dosing regimens (500 mg q8h, 1 g q8h, 2 g q8h, 500 mg q6h, 1 g q6h) infused over 0.5 and 3 hours. Probability of target attainment (PTA) was calculated using fT > MIC of 40% and 54%. Total body weight and body mass index were 152.3 ± 31.0 kg and 54.7 ± 8.6 kg/m 2 , respectively. Volume of distribution of the central compartment was 13.3 ± 6.7 L, volume of distribution at steady‐state was 37.4 ± 14.7 L, and systemic clearance was 10.2 ± 5.0 L/h. At an MIC of 2 µg/mL, PTA was ≥90% for 4/5 and 2/5 regimens infused over 0.5 hours and for 5/5 and 4/5 regimens infused over 3 hours at 40% and 54% fT > MIC, respectively. Standard doses achieve adequate exposures for susceptible bacteria at a pharmacodynamic target of 40% fT > MIC. Higher doses or prolonged infusion regimens are needed at the higher pharmacodynamic target.