Pharmacodynamic (PD) target attainment (TA) in normal size (N), OBESE (OB) and morbidly obese (Mob) healthy volunteers (HV) receiving one gram doses of ertapenem (ETP)

Background Obesity prevalence is rising, yet little is known about the effects of adiposity on drug disposition and therapeutic outcomes. ETP, a carbapenem with broad antimicrobial activity, is dosed once daily. Efficacy is predicted by time of free drug concentration above the minimum inhibitory concentration (T>MIC) with 40% and 20% generally considered PD targets for bactericidal and bacteriostatic activity respectively. Methods 30 HVs (50% M/F) in 3 groups (10/group) of normal body mass index (BMI 18.5–24.9)[34 (8.3) yrs], obese (BMI 30–39.9)[41.8 (5.7) yrs] and morbidly obese (BMI≥ 40)[35.9 (7) yrs] received 1 gm ETP infused over 30 minutes. Serum ETP was obtained at baseline and 12 times/24 hrs. Free drug %T>MIC (using 95% protein binding) was calculated for each HV for susceptible MICs (≤ 2 ug/ml). Kruskal-Wallis ANOVA was used to test for differences in %T>MIC between the groups at each MIC. Data are presented as mean± SD. Results (see Table) Conclusions No significant differences were noted among the groups at MICs≤1. Although a difference was found at MIC=2, clinical significance is uncertain. ETP dosage modifications based on BMI may not be required. At MICs ≥2 ug/mL, larger doses of ETP may be needed in all BMI groups to attain desired PD targets. Clinical Pharmacology & Therapeutics (2005) 77, P20–P20; doi: 10.1016/j.clpt.2004.11.076 Free Drug %T>MIC BMI GROUP MIC (ug/mL) 0.25 0.5 1 2 N 64.2 (2.4) 50.2 (1.7) 36.1 (1.0) 22.1 (0.6) OB 61.3 (2.0) 47.4 (1.5) 33.5 (1.1) 19.6 (0.8) MOB 64.5 (2.6) 49.1 (2.0) 33.6 (1.4) 18.1 (0.9) p > 0.05 p > 0.05 p > 0.05 p = 0.005