• Michael B Kays, Megan R Fleming, S Christian Cheatham, Eun Kyoung Chung, and Joetta M Juenke.
• Purdue University College of Pharmacy, Indianapolis and West Lafayette, IN, USA.
• Ann Pharmacother. 2014 Feb 1; 48 (2): 178-86.

BackgroundAntimicrobial pharmacokinetic and pharmacodynamic data are limited in obesity.ObjectiveTo evaluate the steady-state pharmacokinetics and pharmacodynamics of doripenem and meropenem in obese patients hospitalized on a general ward.MethodsPatients with a body mass index (BMI) ≥40 kg/m² or total body weight (TBW) ≥100 pounds over their ideal body weight randomly received doripenem 500 mg (1-hour infusion) or meropenem 1 g (0.5-hour infusion) every 8 hours. Differences in pharmacokinetic parameters were determined by unpaired t test. Monte Carlo simulations were performed for 500 mg and 1 g every 8 hours, infused over 1 and 4 hours for doripenem and 0.5 and 3 hours for meropenem. Probability of target attainment (PTA) was calculated using a pharmacodynamic target of 40% fT > MIC (free drug concentrations above the minimum inhibitory concentration [MIC]), and cumulative fraction of response (CFR) was calculated using MIC data for 8 Gram-negative pathogens.ResultsTwenty patients were studied. Volume of distribution at steady state, corrected for TBW, was significantly larger (0.18 ± 0.04 vs 0.13 ± 0.05 L/kg, P = .048) and systemic clearance was significantly faster for doripenem (11.7 ± 4.1 vs 8.1 ± 2.6 L/h, P = .03). PTA was >90% for all regimens at MICs ≤2 µg/mL. CFR was >90% for all regimens against 6 enteric Gram-negative pathogens and for 3 of 4 regimens for each drug against Pseudomonas aeruginosa.ConclusionsDoripenem and meropenem pharmacokinetics differ in obesity. However, currently approved dosing regimens provide adequate pharmacodynamic exposures for susceptible bacteria in obese patients.

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