A phase I clinical study: Evaluation of safety, tolerability, and population pharmacokinetic-pharmacodynamic target attainment analysis of etimicin sulfate among healthy chinese participants.

Background: This phase I clinical study aimed to assess the safety, tolerability, and population pharmacokinetic-pharmacodynamics (PK-PD) target attainment analysis of etimicin sulfate in healthy participants, and to provide scientific reference for further development of clinical breakpoints.
Methods: A total of 24 healthy Chinese subjects were enrolled in this study and received an etimicin sulfate infusion. A population PK model was constructed for the estimation of the PK profiles of etimicin sulfate. The area under the concentration-time curve divided by the minimum inhibitory concentration (AUC _0-24h /MIC) and the peak concentration divided by the MIC (C _max /MIC) were selected as the PK/PD indices. The probability of target attainment (PTA) was calculated for each designed dosing regimen using Monte Carlo simulations. The minimum MIC value with a PTA ≥ 90% for each regimen was considered as the PK/PD cutoff values.
Results: Etimicin sulfate demonstrated safety, tolerability, and predictable PK characteristics. No deaths or serious adverse events were reported. Seven treatment-emergent adverse events (TEAEs) were reported by five participants; all TEAEs were minor and were rapidly relieved. A two-compartment model was developed and validated for describing the PK features of etimicin sulfate among Chinese healthy participants. The diagnostic goodness-of-fit plots and visual predictive check plots showed that this developed model could describe these data well.
Conclusions: The PTA results showed that etimicin sulfate provided clinical improvement against strains with an MIC of 0.5-1 mg/L and below, and antibacterial effect against strains with an MIC of 0.25 mg/L and below. However, etimicin sulfate had limited clinical efficacy for clinical isolates with MIC values > 1 mg/L.
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