Steady-State Pharmacokinetics and Pharmacodynamics of Meropenem in Morbidly Obese Patients Hospitalized in an Intensive Care Unit

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 40kg/m(2) received meropenem 500mg or 1g q6h, infused over 0.5hours. Pharmacokinetic parameters were estimated, and Monte Carlo simulations were performed for 5 dosing regimens (500mg q8h, 1g q8h, 2g q8h, 500mg q6h, 1g q6h) infused over 0.5 and 3hours. Probability of target attainment (PTA) was calculated using fT>MIC of 40% and 54%. Total body weight and body mass index were 152.3 +/- 31.0kg and 54.7 +/- 8.6kg/m(2), respectively. Volume of distribution of the central compartment was 13.3 +/- 6.7L, volume of distribution at steady-state was 37.4 +/- 14.7L, and systemic clearance was 10.2 +/- 5.0L/h. At an MIC of 2 mu g/mL, PTA was 90% for 4/5 and 2/5 regimens infused over 0.5hours and for 5/5 and 4/5 regimens infused over 3hours 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.