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      • Pharmacokinetics, Safety, and Tolerability of Tedizolid Phosphate After Single-dose Administration in Healthy Korean Male Subjects

        Kim, Yun,Kim, Anhye,Lee, SeungHwan,Choi, Sung-Hak,Lee, Dae Young,Song, Ji-Su,Lee, Howard,Jang, In-Jin,Yu, Kyung-Sang Elsevier 2017 Clinical therapeutics Vol.39 No.9

        <P><B>Abstract</B></P> <P><B>Purpose</B></P> <P>Tedizolid phosphate is a next-generation oxazolidinone prodrug that is transformed into the active moiety tedizolid. Its indication is acute bacterial skin and skin structure infections caused by gram-positive species, including methicillin-resistant <I>Staphylococcus aureus</I>. Although tedizolid phosphate has been marketed in Korea, no data on the pharmacokinetic (PK) properties or tolerability of tedizolid phosphate in Korean subjects are available. This study was designed to evaluate the PK properties, oral bioavailability, and tolerability with a single-dose oral and intravenous administration of tedizolid phosphate in healthy Korean male subjects.</P> <P><B>Methods</B></P> <P>A block-randomized, double-blind, placebo-controlled, single-dose study was conducted in 3 groups (200, 400, and 600 mg; 10 subjects in each group). In the second part of the study, subjects from the 200-mg group received administration orally and intravenously (1-hour infusion) via 2-way crossover for the evaluation of absolute bioavailability. There was a 7-day washout period between treatments in the absolute bioavailability part of the study. Serial blood samples for PK analysis were collected for up to 72 hours. Tolerability was assessed by analysis of adverse events.</P> <P><B>Findings</B></P> <P>Thirty healthy Korean subjects completed the study and were included in the PK and tolerability analyses. Tedizolid phosphate was rapidly converted into tedizolid. After a single oral dose, the T<SUB>max</SUB> of tedizolid was observed to be 1.5 to 2.5 hours, and the plasma concentration–time curve of tedizolid showed a 2-phase elimination pattern, with a half-life of ~11 hours. Dose-dependent increases were observed in the AUC<SUB>last</SUB> value (29,441–78,062 μg · h/L) and in the C<SUB>max value (</SUB>2679–6980 μg/L) with the administration of tedizolid phosphate 200 to 600 mg PO. The absolute bioavailability of tedizolid was 95.2% (90% CI, 92.7%–97.8%) in the 200-mg administration group. There were no serious adverse events or clinically significant changes in the tolerability assessment.</P> <P><B>Implications</B></P> <P>Tedizolid phosphate at doses of up to 600 mg was well-tolerated in these healthy Korean male subjects. Tedizolid shows dose linearity with oral administration, and no dose adjustment of tedizolid phosphate 200 mg would be needed when switching administration routes. ClinicalTrials.gov identifier: NCT02097043.</P>

      • KCI등재

        In Vitro Activity of Tedizolid Against Gram-Positive Bacteria in Patients With Skin and Skin Structure Infections and Hospital-Acquired Pneumonia: A Korean Multicenter Study

        이양순,용동은,이경원,홍성국,최성학,임원빈 대한진단검사의학회 2015 Annals of Laboratory Medicine Vol.35 No.5

        We compared the activities of tedizolid to those of linezolid and other commonly used antimicrobial agents against gram-positive cocci recovered from patients with skin and skin structure infections (SSSIs) and hospital-acquired pneumonia (HAP) in Korean hospitals. Gram-positive isolates were collected from 356 patients with SSSIs and 144 patients with HAP at eight hospitals in Korea from 2011 to 2014. SSSIs included impetigo, cellulitis, erysipelas, furuncles, abscesses, and infected burns. Antimicrobial susceptibility was tested by using the CLSI agar dilution method. All of the gram-positive isolates were inhibited by ≤1 μg/mL tedizolid. The minimum inhibitory concentration [MIC]90 of tedizolid was 0.5 μg/mL for methicillin-resistant Staphylococcus aureus, which was 4-fold lower than that of linezolid. Tedizolid may become a useful option for the treatment of SSSIs and HAP caused by gram-positive bacteria.

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        Treatment of Recurrent Severe Cellulitis with a Pill in Pocket Approach

        Doub James B. 대한감염학회 2022 Infection and Chemotherapy Vol.54 No.2

        Cellulitis is a common condition that plagues healthcare systems and is associated with significant healthcare costs and resource allocations. With ample antimicrobial therapy this infectious syndrome can be easily treated but recurrence is common. Many conditions predispose patients to be at risk for recurrent cellulitis with chronic lymphoedema being a significant risk factor secondary to pooling of lymphatic fluid and impaired local immune responses. Moreover, patients with chronic lymphoedema can be at risk for acute onset of severe cellulitis requiring urgent medical evaluation and treatment. Consequently, to prevent recurrent cellulitis episodes, the use of long-term oral antibiotics has been advocated, but when recurrences occur despite long-term antibiotic use limited options are available. In this case report, a unique treatment approach for preventing severe cellulitis is discussed with a pill in the pocket approach with the use of oral tedizolid. This has thwarted the need for recurrent hospitalizations and reduced health care costs for this individual patient. Herein this treatment approach is discussed as is the rationale for using tedizolid instead of other antibiotics.

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