title: Clinical dose findings of sitafloxacin treatment: pharmacokinetic-pharmacodynamic analysis of two clinical trial results for community-acquired respiratory tract infections.
abstract: The adequacy of sitafloxacin clinical dose regimens was assessed by comparing the efficacy of the administration of 100 mg sitafloxacin once daily (100 mg qd group) and 50 mg sitafloxacin twice daily (50 mg bid group). Patients with respiratory tract infections caused by pneumococci were orally treated with sitafloxacin (100 mg qd or 50 mg bid) for 7 days. The clinical efficacy, pneumococci eradication rate, safety, and pharmacokinetic and pharmacodynamic indices of the two groups were then assessed. The clinical efficacy was 93.5 % in both groups. The pneumococci eradication rate was 98.2 % in the 100 mg qd group and 92.7 % in the 50 mg bid group. The mean of the free AUC0-24h divided by the minimum inhibitory concentration (MIC) (fAUC0-24h/MIC) did not differ significantly between the 100 mg qd (103.24) and the 50 mg bid groups (105.25). The mean of the free C peak divided by the MIC (fC peak/MIC) was higher in the 100 mg qd group (10.19) than in the 50 mg bid group (6.53). The pathogen eradication rate was 98.9 % (89/90) when the fAUC0-24h/MIC was greater than 30, and the eradication rate was 98.9 % (89/90) when the fC peak/MIC was greater than 2. The incidences of adverse drug reactions were 33.7 % in the 100 mg qd group and 40.4 % in the 50 mg bid group. No obvious differences in the efficacy and safety were observed between the dosage groups. For cases in which a sufficiently high C peak is necessary to ensure the susceptibility of the pathogens to the drug, 100 mg sitafloxacin once daily should be administered.
authors.affiliation: Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. s-kohno@nagasaki-u.ac.jp
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Niki
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Kadota
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Kaku
authors.forename: Akira
authors.initials: A
authors.lastname: Watanabe
authors.forename: Nobuki
authors.initials: N
authors.lastname: Aoki
authors.forename: Seiji
authors.initials: S
authors.lastname: Hori
authors.forename: Jiro
authors.initials: J
authors.lastname: Fujita
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tanigawara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C076246:sitafloxacin