Pharmacokinetics of Tedizolid Following Oral Administration: Single and Multiple Dose, Effect of Food, and Comparison of Two Solid Forms of the Prodrug

OBJECTIVES The single- and multiple-dose pharmacokinetics (PK) of tedizolid were examined after oral administration of tedizolid phosphate disodium (TPD), including the effect of food on PK. The rela-tive bioavailability of TPD to the free acid tedizolid phosphate was determined to bridge the results of these and other studies to the solid form of the prodrug selected for further development. DESIGN Randomized placebo-controlled, double-blind single- and multiple-ascending dose studies and randomized open-label, crossover food effect and relative bioavailability studies. SETTING Clinical Research Units. PARTICIPANTS Healthy subjects. INTERVENTION Study TR701-101 enrolled 40 subjects in single-ascending dose (200–1200 mg TPD or placebo) and 40 subjects in 21-day multiple-ascending dose (200, 300, or 400 mg TPD once/day; 600 mg linezolid twice/day; or placebo) arms. Study TR701-103 was a food-effect study in 12 sub-jects administered 600 mg TPD. Study TR701-108 was a relative bioavailability study in 12 subjects administered 150-mg tedizolid equivalents as TPD or tedizolid phosphate. MEASUREMENTS AND MAIN RESULTS Plasma concentrations of the prodrug tedizolid phosphate, its active moiety tedizolid, and/or linezolid were collected. After administration of 200 to 600 mg TPD