Population pharmacokinetics and dose optimization of intravenous levofloxacin in hospitalized adult patients
| Main Authors: | Setiawan, Eko, Aziz, Mohd‐Hafiz Abdul, Cotta, Menino Osbert, Susaniwati, Susaniwati, Cahjono, Heru, Sari, Ika Yunita, Wibowo, Tjipto, Marpaung, Ferdy Royland, Roberts, Jason A. |
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| Format: | Article PeerReviewed application/pdf |
| Bahasa: | eng |
| Terbitan: |
Nature Publishing Group
, 2022
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| Subjects: | |
| Online Access: |
http://repository.ubaya.ac.id/41971/ https://www.nature.com/articles/s41598-022-12627-1 |
Daftar Isi:
- Although levofloxacin has been used for the last 25 years, there are limited pharmacokinetic data to guide levofloxacin dosing in adult patients. This study aimed to develop a population pharmacokinetic model of levofloxacin for adult hospitalized patients and define dosing regimens that attain pharmacokinetic/pharmacodynamic target associated with maximum effectiveness. Blood samples were drawn from 26 patients during one dosing interval. Population pharmacokinetic modelling and dosign simulations were performed using Pmetrics®. Pathogen minimum inhibition concentration (MIC) distribution data from the European Committee on Antimicrobial Susceptibility Testing database was used to analyse fractional target attainment (FTA). A two-compartment model adequately described the data. The final model included estimated glomerular filtration rate (eGFR) to describe clearance. The population estimate for clearance was 1.12 L/h, while the volume of distribution in the central compartment and peripheral compartments were 27.6 L and 28.2 L, respectively. Our simulation demonstrated that an area under free concentration-time curve to MIC ≥ 80 was hardly achieved for pathogens with MIC ≥ 1 mg/L. Low FTA against Pseudomonas aeruginosa and Streptococcus pneumoniae were observed for patients with higher eGFR (≥ 80 mL/min/1.73m2). A daily levofloxacin dose of 1000 mg is suggested to maximise the likelihood of efficacy for adult patients.