Vol.73 No.S-1 April 2025
PK/PD profile of the new antibacterial agent cefiderocol
1)Clinical Pharmacology & Pharmacokinetics, Shionogi & Co., Ltd., 1-8 Doshomachi 3-chome, Chuo-ku, Osaka, Japan
Abstract
Cefiderocol (CFDC) has been demonstrated to exhibit excellent antibacterial activity against carbapenem-resistant Gram-negative bacteria in both in vitro and in vivo settings. Phase 1 studies have demonstrated that the Cmax and area under the concentration-time curve (AUC) of CFDC increases in a dose-proportional manner in the range of 100 mg to 2,000 mg, with a half-life of about 2-3 hours. Like other β-lactam antibiotics, CFDC exhibits time-dependent effects and the percentage of the free drug concentration exceeding the MIC (%fT > MIC) is predictive of the drug efficacy. Based on pharmacokinetic/pharmacodynamic modeling, the approved dosage and administration for achieving 100% %fT > MIC for target bacteria susceptible to the drug at a MIC of ≤ 4 μg/mL is 2 g of CFDC administered by intravenous infusion over 3 hours every 8 hours for adults. The dosage and administration schedule of CFDC to achieve an AUC equivalent to that achieved when administered to healthy adults has been established for various subpopulations of patients, including those with impaired renal function, patients with augmented renal function, and children. Therefore, in principle, monitoring of blood drug concentrations is not necessary. Moreover, it has been demonstrated that even when administered at standard doses, the drug can be transferred to the lung tissue and is efficacious for the treatment of patients with severe pneumonia. The pharmacokinetic profile of CFDC allows for its administration to various patient groups, regardless of the renal function, and its efficacy and safety have been confirmed in Phase 1 to 3 clinical trials.
Key word
cefiderocol, Gram-negative bacteria, drug resistant bacteria, β-lactamase, PK/PD
Received
November 12, 2024
Accepted
December 26, 2024
Jpn. J. Chemother. 73 (S-1): 17-23, 2025
