title: Pharmacokinetics of Tedizolid in Morbidly Obese and Covariate-Matched Nonobese Adults.
abstract: Tedizolid is a novel oxazolidinone antimicrobial administered in its prodrug form, tedizolid phosphate, as a fixed once-daily dose. The pharmacokinetics of tedizolid has been studied in a relatively small proportion of morbidly obese (body mass index [BMI] of ≥40 kg/m(2)) adults through population analyses with sparse sampling. The current study compared the intensively sampled plasma pharmacokinetics of tedizolid phosphate and tedizolid in 9 morbidly obese and 9 age-, sex-, and ideal body weight-matched nonobese (BMI, 18.5 to 29.9 kg/m(2)) healthy adult (18 to 50 years of age) volunteers after administration of a single intravenous dose of tedizolid phosphate. The median (range) weights were 72.6 kg (58.9 to 89.5 kg) and 117 kg (102 to 176 kg) for the mostly female (77.8%) nonobese and morbidly obese adults, respectively. Tedizolid phosphate concentrations were below the limit of quantitation in a majority of subjects after the 2-h time point. The tedizolid median (range) maximum concentration of drug in plasma (Cmax) and area under the concentration-time curve from 0 h to infinity (AUC0-∞) were 2.38 (1.28 to 3.99) mg/liter and 26.3 (18.4 to 43.2) h · mg/liter, respectively, for morbidly obese subjects, and these were nonsignificantly different (P ≥ 0.214) from the values for nonobese subjects. Similarly, the volumes of distribution (Vz) (P = 0.110) and clearance (CL) values (P = 0.214) were comparable between groups. Nearly identical (P = 0.953) median tedizolid half-lives of approximately 12 h were observed for both groups. Tedizolid Vz and CL scaled with body weight, but not proportionately. The small and nonsignificant differences in tedizolid AUC0-∞ values between morbidly obese and nonobese subjects suggest that dose modification is not necessary for morbidly obese adults. (This study has been registered at ClinicalTrials.gov under number NCT02342418.).
authors.affiliation: Albany College of Pharmacy and Health Sciences, Albany, New York, USA amitpai@umich.edu.
authors.forename: Manjunath P
authors.initials: MP
authors.lastname: Pai
mesh_terms: D000293:Adolescent; D000328:Adult; D049628:Body Size; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000188:drug therapy* / Q000378:metabolism*; D023303:Oxazolidinones / Q000009:adverse effects / Q000493:pharmacokinetics*; D013777:Tetrazoles / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D023303:Oxazolidinones; D013777:Tetrazoles; C546016:tedizolid