Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid.
Bottom Line: Treatment-related adverse events occurred in 41% of subjects.Most adverse events were related to infusion site and became more frequent with multiple dosing.These results from a population of healthy volunteers support once/day dosing of tedizolid phosphate 200 mg with both the oral and IV formulations, without the need for dose adjustment when switching administration routes.
Affiliation: Cubist, San Diego, California.Show MeSH
Related in: MedlinePlus
Mentions: Tolerability and PK of tedizolid were similar for the three infusion regimens, reaching similar peak concentrations when infused in 250 or 500 ml over 2 hours or in 250 ml over 1 hour (data not shown), leading to the selection of the 250-ml 1-hour infusion for the multiple-dose and bioavailability portions of the study. Unlike levels of the prodrug, plasma tedizolid concentrations increased during the infusion and then reached a plateau (250-ml 1-hr infusion is shown in Figure2). Single doses of IV tedizolid phosphate produced dose-dependent increases in tedizolid (Figure3A, B). Mean tedizolid exposure parameters (AUC and Cmax) increased with ascending doses of tedizolid phosphate (Figure4). Median Tmax values for tedizolid were determined primarily by the length of infusion and ranged from 1.2–2.2 hours (Table2). Mean tedizolid t1/2 values ranged from 9.3–13.4 hours for all doses of tedizolid phosphate. There was a dose-dependent increase in the tedizolid Cmax (range 1.2–5.1 μg/ml) for increasing doses of tedizolid phosphate. Similar results were observed for mean AUC0–t and AUC0–∞. Mean apparent volume of distribution at steady state (Vdss) values ranged from 61.2–74.5 L across groups and were dose independent. Clearance values were generally similar, ranging from 4.8–5.8 L/hour, and also indicated dose independence.