Frontiers in Pharmacology (Oct 2024)
Lefamulin dosing optimization using population pharmacokinetic and pharmacokinetic/pharmacodynamic assessment in Chinese patients with community-acquired bacterial pneumonia
- Xingchen Bian,
- Xingchen Bian,
- Xingchen Bian,
- Nanyang Li,
- Nanyang Li,
- Nanyang Li,
- Yi Li,
- Yi Li,
- Yi Li,
- Xu Zhu,
- Xu Zhu,
- Xu Zhu,
- Jicheng Yu,
- Jicheng Yu,
- Jicheng Yu,
- Yingying Hu,
- Yingying Hu,
- Yingying Hu,
- Haijing Yang,
- Haijing Yang,
- Haijing Yang,
- Qiong Wei,
- Qiong Wei,
- Qiong Wei,
- Xiaojie Wu,
- Xiaojie Wu,
- Xiaojie Wu,
- Jingjing Wang,
- Jingjing Wang,
- Jingjing Wang,
- Guoying Cao,
- Guoying Cao,
- Guoying Cao,
- Jufang Wu,
- Jufang Wu,
- Jufang Wu,
- Yang Wang,
- Jing Zhang,
- Jing Zhang,
- Jing Zhang,
- Jing Zhang,
- Jing Zhang
Affiliations
- Xingchen Bian
- Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai, China
- Xingchen Bian
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Xingchen Bian
- Research Ward of Huashan Hospital, Fudan University, Shanghai, China
- Nanyang Li
- Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai, China
- Nanyang Li
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Nanyang Li
- Research Ward of Huashan Hospital, Fudan University, Shanghai, China
- Yi Li
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Yi Li
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China
- Yi Li
- Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China
- Xu Zhu
- Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai, China
- Xu Zhu
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Xu Zhu
- Research Ward of Huashan Hospital, Fudan University, Shanghai, China
- Jicheng Yu
- Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai, China
- Jicheng Yu
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Jicheng Yu
- Research Ward of Huashan Hospital, Fudan University, Shanghai, China
- Yingying Hu
- Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai, China
- Yingying Hu
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Yingying Hu
- Research Ward of Huashan Hospital, Fudan University, Shanghai, China
- Haijing Yang
- Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai, China
- Haijing Yang
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Haijing Yang
- Research Ward of Huashan Hospital, Fudan University, Shanghai, China
- Qiong Wei
- Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai, China
- Qiong Wei
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Qiong Wei
- Research Ward of Huashan Hospital, Fudan University, Shanghai, China
- Xiaojie Wu
- Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai, China
- Xiaojie Wu
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Xiaojie Wu
- Research Ward of Huashan Hospital, Fudan University, Shanghai, China
- Jingjing Wang
- Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai, China
- Jingjing Wang
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Jingjing Wang
- Research Ward of Huashan Hospital, Fudan University, Shanghai, China
- Guoying Cao
- Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai, China
- Guoying Cao
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Guoying Cao
- Research Ward of Huashan Hospital, Fudan University, Shanghai, China
- Jufang Wu
- Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai, China
- Jufang Wu
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Jufang Wu
- Research Ward of Huashan Hospital, Fudan University, Shanghai, China
- Yang Wang
- Sumitomo Pharmaceuticals (Suzhou) Co., Ltd., Shanghai, China
- Jing Zhang
- Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai, China
- Jing Zhang
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Jing Zhang
- Research Ward of Huashan Hospital, Fudan University, Shanghai, China
- Jing Zhang
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China
- Jing Zhang
- Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China
- DOI
- https://doi.org/10.3389/fphar.2024.1456741
- Journal volume & issue
-
Vol. 15
Abstract
PurposeLefamulin is the first pleuromutilin antibiotic approved for the treatment of community-acquired 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.MethodsThe 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 q12 h for 1-h, 1.5-h and extended 2-h infusion. Oral administrations of 600 mg q12 h were assessed, considering original and higher plasma protein binding.ResultsLefamulin 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 q12 h via intravenous infusion for 1/1.5/2 h, the probability of target attainments reached 98% at the minimum inhibitory concentration for both 90% S. pneumoniae and S. aureus, considering both original and higher protein binding rates. It is advisable to extend the infusion duration from 1/1.5 h–2 h to minimize the risk of adverse effects at the infusion site. Regardless of fasted or fed conditions, the PTAs for 600 mg q12 h lefamulin via oral administration proved comparable to those for intravenous administration.ConclusionThis study proved that intravenous and oral administrations of lefamulin can reach preclinical PK/PD targets of S. pneumoniae and S. 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
