Abstract
Antimicrobial pharmacokinetic and pharmacodynamic data are limited in obesity. To evaluate the steady-state pharmacokinetics and pharmacodynamics of doripenem and meropenem in obese patients hospitalized on a general ward. Patients 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. Twenty 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. Doripenem and meropenem pharmacokinetics differ in obesity. However, currently approved dosing regimens provide adequate pharmacodynamic exposures for susceptible bacteria in obese patients.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call