Population pharmacokinetics and pharmacodynamics of eravacycline in patients with complicated intra-abdominal infections and community acquired bacterial pneumonia: Support for a fixed-dose treatment regimen.

Eravacycline is a tetracycline used for the treatment of complicated intra-abdominal infections (cIAI) and has the potential to treat community-acquired bacterial pneumonia (CABP). The approved regimen for cIAI is 1 mg/kg (Q12h). However, studies have reported the inconvenience of drug preparation based on body weight (BW) and wastage of the drug, because the specification is 50 mg per vial. A fixed-dose regimen based on population pharmacokinetic/pharmacodynamic (PK/PD) modeling and simulations may address these limitations. Three clinical trials were performed in healthy Chinese participants and patients with cIAI and CABP. A PopPK model was developed using nonlinear mixed-effects modeling. A fixed-dose regimen in patients with a BW of 40-175 kg was recommended by the Monte Carlo simulation. The probability of target attainment and the cumulative fraction of response (CFR) were calculated. Overall, 79 participants were included in the study. BW, sex, albumin level, and subject type were covariates on PK. When patients received a fixed-dose, AUC was 80-125% in patients with BW 60 kg receiving 1 mg/kg eravacycline. The PK/PD cutoff and CFR for the fixed-dose regimens were close to those of 1 mg/kg. The recommended fixed-doses (body weight range) were 50 mg (40-60 kg), 75 mg (60-100 kg), 100 mg (100-125 kg), 125 mg (125-150 kg), and 150 mg (150-175 kg). This should be used with caution in patients with BW >137 kg because the actual PK data were not collected. Nonetheless, fixed dosing is more convenient for drug preparation, avoids drug waste, and reduces medical costs compared with weight-based dosing. Trial Registration Number: ChiCTR1900022906, ChiCTR1900022060, and ChiCTR2200055666.