-Original-

Investigation of the Optimal Interval of Perioperative Serum Flomoxef Administration in Hepatobiliary-Pancreatic Surgery

Yoko Takayama^1,2, Toshiaki Komatsu³, Satomi Tsumuraya⁴, Hidefumi Kubo⁵, Nobuyuki Nishizawa⁵, Hiroshi Tajima⁵, Takashi Kaizu⁵, Katsuya Otori⁶, Hirotsugu Okamoto⁷, Yusuke Kumamoto⁵ and Hideaki Hanaki⁸

¹Department of Infection Control and Infectious Diseases, Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Kanagawa, Japan
²Department of Infection Control and Prevention, Kitasato University Hospital, Kanagawa, Japan
³Department of Pharmacy, Kitasato University Hospital, Kanagawa, Japan
⁴Sogo Medical Company Limited, Tokyo, Japan
⁵Department of General-Pediatric-Hepatobiliary Pancreatic Surgery, Kitasato University School of Medicine, Kanagawa, Japan
⁶Pharmacy Practice and Science I, Research and Education Center for Clinical Pharmacy, Kitasato University School of Pharmacy, Tokyo, Japan
⁷Department of Anesthesiology, Kitasato University School of Medicine, Kanagawa, Japan
⁸Infection Control Research Center, The Omura Satoshi Memorial Institution, Kitasato University, Tokyo, Japan

Background: Perioperative prophylactic antimicrobials are re-administered at intervals of twice their half-life. However, the actual concentrations of antimicrobial agents and the degree of elevation remain unelucidated.
Methods: This prospective cohort study was conducted at a single tertiary care center. Serum concentrations were evaluated in patients who underwent hepatobiliary-pancreatic surgery between April 2019 and December 2020 and received an additional dose of flomoxef (FMOX) every 3 h or 5 h during the surgical procedure based on their renal function.
Results: Among the 31 participants, 25 and six received FMOX every 3 h and 5 h, respectively. Analysis based on renal function revealed median FMOX concentrations of 9.88 mg/L and 9.85 mg/L (p = 0.09) for patients with creatinine clearance (Ccr) >60 mL/min and 14.26 mg/L and 20.03 mg/L (p = 0.02) for the patients with Ccr ≤60 mL/min at 3 h and 6 h, respectively, with notable elevation at Ccr ≤60 mL/min. Moreover, the serum FMOX concentration at 6 h for the 3-h dosing patients with Ccr ≤60 mL/min was significantly higher than the concentration at 5 h for the 5-h dosing patients with Ccr ≤60 mL/min (20.03 mg/L vs. 12.85 mg/L, p = 0.04). Although serum concentrations at 3-h and 6-h intervals did not differ significantly in patients with Ccr ≥60 mL/min, these significantly increased in patients with Ccr <60 mL/min.
Conclusions: Administering FMOX every 3 h when Ccr is ≥60 mL/min and every 5 h when Ccr is <60 mL/min are appropriate.

J Nippon Med Sch 2025; 92: 196-203

Keywords
serum concentration, flomoxef, dosing interval, renal function, hepatobiliary-pancreatic surgery

Correspondence to
Yoko Takayama, Department of Infection Control and Infectious Diseases, Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan
yoko@med.kitasato-u.ac.jp

Received, October 20, 2024
Accepted, January 15, 2025