Population pharmacokinetics and dose optimization of intravenous levofloxacin in hospitalized adult patients

Setiawan, Eko and Aziz, Mohd‑Hafiz Abdul and Cotta, Menino Osbert and Susaniwati, Susaniwati and Cahjono, Heru and Sari, Ika Yunita and Wibowo, Tjipto and Marpaung, Ferdy Royland and Roberts, Jason A. (2022) Population pharmacokinetics and dose optimization of intravenous levofloxacin in hospitalized adult patients. Scientific reports, 12 (8930). ISSN 2045-2322

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	Population pharmacokinetic, levofloxacin
Subjects:	R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica
Divisions:	Faculty of Business and Economic > Department of Management
Depositing User:	Eko Setiawan 206023
Date Deposited:	14 Jun 2022 10:24
Last Modified:	20 Mar 2023 04:22
URI:	http://repository.ubaya.ac.id/id/eprint/41971

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