title: Steady-state pharmacokinetics and pharmacodynamics of meropenem in morbidly obese patients hospitalized in an intensive care unit.
abstract: 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.
authors.affiliation: Department of Pharmacy, Franciscan St. Francis Health, Indianapolis, IN, USA.
authors.forename: S Christian
authors.initials: SC
authors.lastname: Cheatham
authors.forename: Megan R
authors.initials: MR
authors.lastname: Fleming
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Healy
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Chung
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Shea
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Humphrey
authors.forename: Michael B
authors.initials: MB
authors.lastname: Kays
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004334:Drug Administration Schedule; D005260:Female; D006760:Hospitalization; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008954:Models, Biological; D009010:Monte Carlo Method; D009767:Obesity, Morbid / Q000188:drug therapy / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D013845:Thienamycins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem
keywords: meropenem; obesity; pharmacodynamics; pharmacokinetics