Population Pharmacokinetic Model and Limited Sampling Strategies for Personalized Dosing of Levofloxacin in Tuberculosis Patients

Levofloxacin is an antituberculosis drug with substantial interindividual pharmacokinetic variability; therapeutic drug monitoring (TDM) could therefore be helpful to improve treatment results. TDM would be more feasible with limited sampling strategies (LSSs), a method to estimate the area under th...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2018-12, Vol.62 (12)
Main Authors: van den Elsen, Simone H J, Sturkenboom, Marieke G G, Van't Boveneind-Vrubleuskaya, Natasha, Skrahina, Alena, van der Werf, Tjip S, Heysell, Scott K, Mpagama, Stellah, Migliori, Giovanni B, Peloquin, Charles A, Touw, Daan J, Alffenaar, Jan-Willem C
Format: Article
Language:English
Subjects:
Antitubercular Agents
Clinical Therapeutics
Levofloxacin
Models, Statistical
Mycobacterium tuberculosis
Precision Medicine
Tuberculosis, Pulmonary
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Summary:Levofloxacin is an antituberculosis drug with substantial interindividual pharmacokinetic variability; therapeutic drug monitoring (TDM) could therefore be helpful to improve treatment results. TDM would be more feasible with limited sampling strategies (LSSs), a method to estimate the area under the concentration curve for the 24-h dosing interval (AUC ) by using a limited number of samples. This study aimed to develop a population pharmacokinetic (popPK) model of levofloxacin in tuberculosis patients, along with LSSs using a Bayesian and multiple linear regression approach. The popPK model and Bayesian LSS were developed using data from 30 patients and externally validated with 20 patients. The LSS based on multiple linear regression was internally validated using jackknife analysis. Only clinically suitable LSSs (maximum time span, 8 h; minimum interval, 1 h; 1 to 3 samples) were tested. Performance criteria were root-mean-square error (RMSE) of
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.01092-18