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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacology of Infectious Diseases
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1456741

Lefamulin dosing optimization using population pharmacokinetic and pharmacokinetic/pharmacodynamic assessment in Chinese patients with communityacquired bacterial pneumonia

Provisionally accepted
Xingchen Bian Xingchen Bian 1Nanyang Li Nanyang Li 1Yi Li Yi Li 1Xu Zhu Xu Zhu 1Jicheng Yu Jicheng Yu 1Yingying Hu Yingying Hu 1Haijing Yang Haijing Yang 1Qiong Wei Qiong Wei 1Xiaojie Wu Xiaojie Wu 1Jingjing Wang Jingjing Wang 1Guoying Cao Guoying Cao 1Jufang Wu Jufang Wu 1Yang Wang Yang Wang 2Jing Zhang Jing Zhang 1*
  • 1 Huashan Hospital, Fudan University, Shanghai, China
  • 2 Sumitomo Pharma (Suzhou) Co., Ltd, Shanghai, China

The final, formatted version of the article will be published soon.

    Purpose Lefamulin is the first pleuromutilin antibiotic approved for the treatment of communityacquired bacterial pneumonia (CABP). However, the pharmacokinetic/pharmacodynamic (PK/PD) characteristics in Chinese CABP patients are not fully understood. This study aimed to evaluate its microbiological efficacy against Streptococcus pneumoniae and Staphylococcus aureus via PK/PD analysis.The population PK (PopPK) model, established with foreign data was validated using data from Chinese CABP patients. PK/PD analysis was conducted for the intravenous administration of 150 mg q12h for 1-h, 1.5-h and extended 2-h infusion. Oral administrations of 600 mg q12h were assessed, considering original and higher plasma protein binding.Lefamulin displayed similar PK characteristics in both Chinese and Western populations.The PopPK model effectively predicted lefamulin concentrations in Chinese CABP patients. Under the dosage regimen of 150 mg q12h via intravenous infusion for 1/1.5/2h, the probability of target attainments reached 98% at the minimum inhibitory concentration for both 90% Streptococcus pneumoniae and Staphylococcus aureus, considering both original and higher protein binding rates.It is advisable to extend the infusion duration from 1/1.5 h to 2 h to minimize the risk of adverse effects at the infusion site. Regardless of fasted or fed conditions, the PTAs for 600 mg q12h lefamulin via oral administration proved comparable to those for intravenous administration.This study proved that intravenous and oral administrations of lefamulin can reach preclinical PK/PD targets of Streptococcus pneumoniae and Staphylococcus aureus. These findings support the optimal use of lefamulin for the safe and effective treatment of Chinese CABP patients.

    Keywords: Lefamulin, Chinese population, Population pharmacokinetic, pharmacokinetic/pharmacodanamic, Community-acquired bacterial pneumonia

    Received: 29 Jun 2024; Accepted: 26 Sep 2024.

    Copyright: © 2024 Bian, Li, Li, Zhu, Yu, Hu, Yang, Wei, Wu, Wang, Cao, Wu, Wang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jing Zhang, Huashan Hospital, Fudan University, Shanghai, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.