Eravacycline, a parent tetracycline antibiotic, has been approved for the treatment of complicated intra-abdominal infections (cIAI) [1] and has therapeutic potential for the treatment of community-acquired bacterial pneumonia (CABP) [2]. The recommended dose of eravacycline for patients with cIAI aged ≥ 18 years is 1 mg/kg, administered as an intravenous (IV) infusion over approximately 60 min every 12 h for 4–14 days [1].

Eravacycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit, blocking the entry of amino-acyl tRNA molecules into the A site of the ribosome, thereby preventing the incorporation of amino acid residues into elongating peptide chains. Eravacycline is highly active in vitro against nosocomial and community-acquired methicillin-susceptible or -resistant Staphylococcus aureus strains, vancomycin-susceptible or -resistant Enterococcus faecium, Enterococcus faecalis, and penicillin-susceptible or -resistant Streptococcus pneumoniae. Acinetobacter baumannii, a clinical species of Enterobacteriaceae, ESBL-producing and/or carbapenem-resistant strains of Escherichia coli, Klebsiella pneumoniae, Proteus spp, Providencia spp, Enterobacter spp. and other anaerobes are also sensitive to eravacycline [3].

A phase I study investigated the pharmacokinetics (PK) of eravacycline in healthy participants following a single administration of 1–3 mg/kg [4] and reported that the area under the curve (AUC) and peak concentration (Cmax) were linearly correlated with the dose. Eravacycline had a plasma protein-binding rate of 79–90% at a concentration of 0.1–10 mg/L, which increased with concentration. The Cmax and area under the curve from 0 to 12 h (AUC0-12h) were 2.1 mg/L and 4.3 h·mg/L following first administration at a dose of 1 mg/kg Q12h, respectively. The peak concentration at steady state (Cmax,ss) and area under the curve from 0 to 12 hat steady state (AUC0-12h,ss) were 1.8 mg/L and 6.3 h·mg/L, respectively, while the accumulation index (AC) was 1.45 [1,5]. The apparent distribution volume at steady state (Vss) was approximately 321 L, while the mean terminal elimination half-life (T1/2) was 20 h. The total and renal clearance were 13.5 and 3.0–3.5 L/h, respectively. Additionally, 34% of eravacycline was excreted in urine and 47% was excreted in feces following a single administration of 60 mg with radioactive labeling. Eravacycline mainly undergoes oxidative metabolism via the cytochrome P450 3A4 and flavin-containing monooxygenase. Furthermore, a study reported that concomitant administration of rifampin and eravacycline accelerated the elimination of eravacycline [6]. A population pharmacokinetic (PopPK) study of IV eravacycline demonstrated a mean Vss of 320 L or 4.2 L/kg, a mean T1/2 of 48 h, and a mean total clearance (CLt) of 13.5 L/h [7]. However, to the best of our knowledge, only one study has reported on the PK of eravacycline in patients with extracorporeal membrane oxygenation and continuous veno-venous hemofiltration [8]. Thus, reports on the PK of eravacycline in patients with CABP and in the Chinese population are lacking.

Although weight-based drug administration has been approved, it results in difficulties in clinical practice. First, weighing patients with dysfunction and severe cIAI or other infections is inconvenient because they often lie in bed. Second, drug waste may exist in low-economic areas and drug vials may be shared among patients. In China, the approved dose for eravacycline is 1 mg/kg and the marketed specification is 50 mg per vial. Thus, drug waste may occur if the patient’s body weight (BW) is not an integral multiple of 50 kg, and shared use is not possible. Consequently, the desire for a fixed recommended dose based on BW or range of BWs has been expressed in real-world clinical practice. Therefore, we aimed to utilize existing clinical studies in the Chinese population for PopPK and pharmacokinetic/pharmacodynamic (PK/PD) analyses of eravacycline. Our results suggest the need for an optimized fixed-dose regimen with easier clinical operation.