Pharmacokinetics of Telavancin at Fixed Doses in Normal Body Weight and Obese (Classes I, II, and III) Adult Subjects [PublishAheadOfPrint]

A recommended total body weight (TBW) dosing strategy for telavancin may not be optimal in obese patients. The primary objective of this study was to characterize and compare the pharmacokinetics (PK) of telavancin across four body size groups: normal to overweight and obesity classes I, II, and III. Healthy adult subjects (n=32) received a single, weight-stratified, fixed dose of 500 mg (n=4), 750 mg (n=8) or 1000 mg (n=20) of telavancin. Noncompartmental PK analyses revealed subjects with body mass index (BMI) ≥ 40 kg/m² had a higher volume of distribution (16.24 ± 2.7 L) than subjects with BMI < 30 kg/m² (11.71 ± 2.6 L). The observed AUC_0- ranged from 338.1 to 867.3 mg·h/L, with the lowest exposures in subjects who received 500 mg. AUC_0- values were similar among obese subjects who received 1000 mg. A two-compartment population PK model best described the plasma concentration-time profile of telavancin when adjusted body weight (ABW) was included as a predictive covariate. Fixed doses of 750 mg and 1000 mg had similar target attainment probabilities for efficacy as 10 mg/kg doses based on ABW and TBW, respectively. However, the probability of achieving a target AUC_0-24 ≥ 763 mg·h/L associated with acute kidney injury was highest (19.7%) with TBW-simulated dosing and lowest (0.4%) at the 750 mg dose. These results suggest a fixed dose of 750 mg as a safe and effective alternative to telavancin doses based on TBW or ABW for treatment of obese patients with normal renal function and Staphylococcus aureus infections.

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