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Pharmacokinetics and safety of colistin sulfate after single and multiple intravenous doses in healthy Chinese subjects.
Huang, Xiaolan; Liu, Xiaofen; Fan, Yaxin; Wang, Yu; Guo, Beining; Wang, Jingjing; Yu, Jicheng; Wei, Qiong; Wu, Xiaojie; Huang, Haihui; Zhang, Jing.
Afiliación
  • Huang X; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Antibiotic Clinical Pharmacology of the National Health Commission, Shanghai, China;; National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
  • Liu X; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Antibiotic Clinical Pharmacology of the National Health Commission, Shanghai, China;; National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
  • Fan Y; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Antibiotic Clinical Pharmacology of the National Health Commission, Shanghai, China;; National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
  • Wang Y; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Antibiotic Clinical Pharmacology of the National Health Commission, Shanghai, China;; National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
  • Guo B; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Antibiotic Clinical Pharmacology of the National Health Commission, Shanghai, China;; National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
  • Wang J; Key Laboratory of Antibiotic Clinical Pharmacology of the National Health Commission, Shanghai, China;; National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China;; Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai,
  • Yu J; Key Laboratory of Antibiotic Clinical Pharmacology of the National Health Commission, Shanghai, China;; National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China;; Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai,
  • Wei Q; Key Laboratory of Antibiotic Clinical Pharmacology of the National Health Commission, Shanghai, China;; National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China;; Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai,
  • Wu X; Key Laboratory of Antibiotic Clinical Pharmacology of the National Health Commission, Shanghai, China;; National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China;; Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai,
  • Huang H; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Antibiotic Clinical Pharmacology of the National Health Commission, Shanghai, China.
  • Zhang J; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Antibiotic Clinical Pharmacology of the National Health Commission, Shanghai, China;; National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China;; Clini
Int J Antimicrob Agents ; : 107326, 2024 Sep 12.
Article en En | MEDLINE | ID: mdl-39276945
ABSTRACT

BACKGROUND:

Increasing antimicrobial resistance has led to the revival of the polymyxins as a last-resort therapeutic option for multidrug-resistant Gram-negative bacterial infections. A parenteral formulation of colistin sulfate is available solely in China. While the onset of action of IV colistin may occur faster than with its prodrug CMS, its pharmacokinetic (PK) profile remains unclear.

METHODS:

This single-centre, open-label, single- and multi-dose, phase 1 trial examined the PKs and safety of colistin sulfate in healthy Chinese adults. Participants received a single 10000 units/kg (equivalent to 0.452 mg/kg) dose of colistin sulfate (single-dose group; n=12) or the same dose q12h for 7 days (multi-dose group, n=12) via a 2-h IV infusion. Colistin concentrations in plasma and urine were determined using LC-MS/MS, and the PK parameters calculated using non-compartmental analysis.

RESULTS:

After a single dose the peak concentration (Cmax), area under the curve from 0 to 12 h (AUC0-12h), terminal half-life (T1/2), volume of distribution (Vd), and total body clearance (CL) of colistin were 1.08 ± 0.18 mg/L, 4.73 ± 0.89 h·mg/L, 3.65 ± 0.55 h, 16.82 ± 2.70 L, and 3.24 ± 0.51 L/h, respectively. No accumulation of colistin was observed after multiple doses. The cumulative urinary recovery of colistin was 0.9 ± 0.7% within 24 h after multi-dose administration. No nephrotoxicity was reported.

CONCLUSIONS:

This study is the first to report colistin PKs in healthy Chinese subjects after single and multiple doses of colistin sulfate. The PK and safety data are required for optimal dose selection in clinical practice.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Int J Antimicrob Agents Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Int J Antimicrob Agents Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos