Optimization of Lefamulin Administration in Patients with Different Liver Functions Based on Monte Carlo Simulations

The objective of this study was to evaluate the efficacy of various intravenous lefamulin dosing regimens against Streptococcus pneumoniae, Staphylococcus aureus, MRSA and MSSA in patients with different liver functions. Monte Carlo simulations (MCSs) were conducted using pharmacokinetic (PK) parameters and pharmacodynamic (PD) data to determine the probabilities of target attainment (PTA) and cumulative fractions of response CFR in terms of area under the concentration curve of the free drug (fAUC)/minimum inhibitory concentration (MIC) targets of lefamulin. According to the results of the MCSs, for patients with normal liver function, the standard dosage regimen of 150 mg q12 h can meet PTA > 90% only when MIC <= 0.125 mg/L. For patients with moderate liver function impairment, the standard dosage can meet PTA > 90% only when MIC <= 0.25 mg/L. For patients with severe liver function impairment, the recommended dosage of 150 mg qd in drug label can achieve good results when MIC <= 0.25 mg/L. As the MIC increases, it may be necessary to combined administration or replacement of other drugs.