Population pharmacokinetics of arbekacin in different infectious disease settings and evaluation of dosing regimens.
The efficacy of arbekacin in patients with MRSA infections is influenced by the peak concentration (Cpeak)/MIC ratio (≧8). A daily arbekacin dose of 4-6 mg/kg is primarily used for the treatment of MRSA infection. However, clinical pharmacokinetic studies of arbekacin that evaluate changes in patients with different infectious diseases have been limited. This study was to evaluate the pharmacokinetics of arbekacin in different infectious diseases and to evaluate its dosing regimens. This work describes a single-centre, retrospective study. The pharmacokinetic parameters of arbekacin were calculated from individual serum-concentration data using WinNonlin ver. 6.3. A total of 331 serum samples were obtained from 170 patients. Our drug concentration-time data were well described by a two-compartment open model. The final model showed that drug clearance was related to creatinine clearance and that the total distribution volume (Vd) was related to actual body weight and the presence of bacteremia. The individual Vd in bacteremia patients was significantly higher than those of other patients (bacteremia: 29.7 ± 0.5 L, pneumonia: 20.8 ± 0.4 L, other infections: 21.4 ± 0.4 L; p < 0.05). Additionally, Monte Carlo simulation showed that target (Cpeak/MIC ≧ 8) attainment was only 10.1%, even at a dose of 6 mg/kg, especially for MRSA bacteremia patients with an arbekacin MIC = 2 μg/mL. In conclusion, our study revealed that the Vd may be higher in bacteremia patients than in patients with other infectious diseases. Therefore, an increase in the daily dose of arbekacin should be considered for bacteremia patients.
Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan; Department of Pharmacy, Aichi Medical University School of Hospital, Japan.
Mao
M
Hagihara
Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan; Department of Pharmacy, Aichi Medical University School of Hospital, Japan.
Hideo
H
Kato
Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Japan; Department of Pharmacy, Aichi Medical University School of Hospital, Japan.
Yukihiro
Y
Hamada
Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Japan.
Jun
J
Hirai
Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
Daisuke
D
Sakanashi
Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
Hiroyuki
H
Suematsu
Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
Naoya
N
Nishiyama
Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
Yusuke
Y
Koizumi
Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
Yuka
Y
Yamagishi
Department of Pharmacy, Aichi Medical University School of Hospital, Japan.
Katsuhiko
K
Matsuura
Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan. Electronic address: mikamo@aichi-med-u.ac.jp.
Hiroshige
H
Mikamo
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism; D003982:Dibekacin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D008875:Middle Aged; D008954:Models, Biological; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000378:metabolism; D055815:Young Adult
D000900:Anti-Bacterial Agents; D003982:Dibekacin; C031986:arbekacin
Arbekacin; Bacteremia; Pneumonia; Population pharmacokinetic analysis