Tedizolid phosphate is a novel oxazolidinone prodrug antibacterial being investigated for the treatment of Gram-positive infections, including those caused by methicillin-resistant Staphylococcus aureus. Tedizolid phosphate is rapidly converted by endogenous phosphatases to tedizolid, the microbiologically active moiety.1,2 In 2 recent Phase 3 trials in patients with acute bacterial skin and skin structure infections (ABSSSI), tedizolid (200 mg once daily for 6 days) demonstrated noninferior efficacy to linezolid (600 mg twice daily for 10 days), and was generally well tolerated.3,4 Obesity is a key patient characteristic shown to alter dose-exposure relationships with some drugs, thus resulting in the need for dose adjustments for this particular patient population. 5 Available data suggest that linezolid systemic exposure is lower in obese than in nonobese patients. 6-9 The reason for this difference has not been determined, and it is not currently known whether linezolid dose modification is warranted in obese patients. Previous studies have shown that, following oral or intravenous (IV) administration of tedizolid phosphate 200 mg, tedizolid exposure in elderly persons, adolescents, and subjects with severe hepatic or renal impairment (including those requiring hemodialysis) was similar to that of control groups.10,11 In the current analysis, the influence of body weight and body mass on tedizolid plasma pharmacokinetics (PK) was evaluated to determine whether plasma exposure parameters of tedizolid are comparable in obese and nonobese individuals.
European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Barcelona, Spain, May 2014
By Shawn Flanagan, Sonia L. Minassian, Julie A. Passarell, Jill B. Fiedler-Kelly, Philippe Prokocimer