Approval for the current study was given by the Ethics Committee of Kamakura Hospital. Two patients with acute osteoarthritis were successfully treated with tedizolid between April 2023 and June 2023. The plasma and synovial fluid concentrations of tedizolid in these two patients (women aged 79 and 73 years, Table 1), who were treated at Kamakura Hospital for osteoarthritis infected with S. aureus, were evaluated after administration of 200 mg once daily by intravenous infusion (at 10 am) for 7 days in case 1 and for 2 days in case 2. The patients provided written informed consent to participate in this study and for its publication. The clinical laboratory results of these two patients over a 2- or 3-week period are shown in Fig. 1A and B. Clinical laboratory data before tedizolid treatment for case 1 were plasma creatinine (0.91 mg/dL), plasma bilirubin (1.6 mg/dL), and platelets (17.1 × 104/µL), whereas those for case 2 were plasma creatinine (0.80 mg/dL), plasma bilirubin (0.6 mg/dL), and platelets (26.6 × 104/µL). Drugs co-administered (per day) during tedizolid treatment in case 1 were candesartan (4 mg), dapagliflozin (5 mg), vildagliptin (100 mg), metformin (1000 mg), and pitavastatin (2 mg), whereas those in case 2 were telmisartan (40 mg), amlodipine (5 mg), loxoprofen (180 mg), lansoprazole (15 mg), and pitavastatin (1 mg). The patients were found to have methicillin-sensitive S. aureus in synovial fluids by outsourced clinical laboratory services.

Clinical laboratory results and measured plasma concentrations of tedizolid (solid circles) in two patients administered 200 mg once daily via intravenous infusion. Levels are shown of C-reactive protein (circles, mg/dL) and white blood cell counts (squares, µL− 1) in the two patients: (A) a 79-year-old woman (48 kg), case 1, and (B) a 73-year-old woman (80 kg), case 2. The measured plasma concentrations of tedizolid (solid circles) in cases 1 (C) and 2 (D) are shown after once-daily administrations. Plasma concentrations of tedizolid (dashed lines) after virtual daily doses were generated using a previously reported one-compartment model [11], using Microsoft Excel

Samples of synovial fluid were obtained from both patients during surgery or knee aspiration, and these, in addition to plasma samples, were analyzed pharmacokinetically. In the preliminary study, plasma samples from two additional patients (an 84-year-old woman, 49 kg, and an 80-year-old woman, 54 kg) were analyzed. Samples (100 µL) of plasma and synovial fluid obtained from the four patients were mixed with an equivalent volume of acetonitrile, and the aqueous supernatant was centrifuged at 15,000 × g for 10 min at 4 °C. Synovial fluid and plasma levels of tedizolid were measured using a reversed-phase, high-performance, liquid chromatography system (Shimadzu, Kyoto, Japan) with a Mightysil RP-18GP Aqua column (5 μm, 150 × 4.6 mm, Kanto Chemical, Tokyo, Japan) equilibrated in a mobile phase comprising 35% CH3CN in 0.1% aqueous phosphoric acid at a flow rate of 1.0 mL/min and a column temperature of 45 °C. Fluorescence monitoring was carried out at excitation and emission wavelengths of 300 and 340 nm [12], respectively, and ultraviolet monitoring was done at 254 nm. The samples (10 µL) were infused using an autosampler. Figure 2 demonstrates typical chromograms of tedizolid in plasma and synovial fluid. The retention time of tedizolid was 15.3 min. For cases 1 and 2, the determined plasma concentrations of tedizolid and the concentration profiles generated using a pharmacokinetic model [set up from a previously described one-compartment model that used the following parameters: a common half-life of 7.1 h (calculated from 6.69 L/h of clearance and median volume of distribution of 69 L), and individual volumes of distributions of 46 and 91 L, respectively, for the body weights of cases 1 and 2 (calculated from 52 L for 5th percentile of 52 kg, 69 L for median of 65 kg, and 88 L for 95th percentile of 78 kg)] are shown in Fig. 1C and D, respectively [11]. The concentrations of tedizolid in plasma samples obtained during surgery for case 1 on day 7 and for case 2 on day 2 were 1.6 and 3.3 µg/mL, respectively. Synovial fluid levels of tedizolid obtained during surgery in case 1 and case 2 were 2.1 and 2.9 µg/mL, respectively; these concentrations represented synovial fluid/plasma ratios of 130% and 88% (Table 1). Data are presented as the mean from triplicate determinations. The biological matrix did not affect the measured concentrations.

Representative chromatograms for tedizolid in plasma and synovial fluid. (A) The patient in case 1 was treated with tedizolid once a day; her plasma samples were analyzed using fluorescence (thin line) and ultraviolet (solid line) detectors. (B) Tedizolid levels in samples of plasma (thin line) and synovial fluid (solid line) were determined using a fluorescence detector. The retention times of tedizolid and tedizolid phosphate derived from a dosage formulation were 15.3 and 12.9 min, respectively