Journal article
Limited sampling strategy and target attainment analysis for levofloxacin in patients with tuberculosis
Antimicrobial agents and chemotherapy, Vol.59(7), pp.3800-3807
07/2015
DOI: 10.1128/AAC.00341-15
PMCID: PMC4468713
PMID: 25870068
Abstract
There is an urgent need to improve and shorten the treatment of tuberculosis (TB) and multidrug resistant tuberculosis (MDR-TB). Levofloxacin, a newer fluoroquinolone, has potent activity against TB both in vitro and in vivo. Levofloxacin dosing can be optimized to improve the treatment of both TB and MDR-TB. Levofloxacin efficacy is linked primarily to the ratio of the area under the concentration-time curve for the free fraction of drug (fAUC) to the MIC. Since obtaining a full-time concentration profile is not feasible in the clinic, we developed a limited sampling strategy (LSS) to estimate the AUC. We also utilized Monte Carlo simulations to evaluate the dosing of levofloxacin. Pharmacokinetic data were obtained from 10 Brazilian TB patients. The pharmacokinetic data were fitted with a one-compartment model. LSSs were developed using two methods: linear regression and Bayesian approaches. Several LSSs predicted levofloxacin AUC with good accuracy and precision. The most accurate were the method using two samples collected at 4 and 6 h (R(2) = 0.91 using linear regression and 0.97 using Bayesian approaches) and that using samples collected at 2 and 6 h (R(2) = 0.90 using linear regression and 0.96 using Bayesian approaches). The 2-and-6-h approach also provides a good estimate of the maximum concentration of the drug in serum (Cmax). Our target attainment analysis showed that higher doses (17 to 20 mg/kg of body weight) of levofloxacin might be needed to improve its activity. Doses in the range of 17 to 20 mg/kg showed good target attainment for MICs from 0.25 to 0.50. At an MIC of 2, poor target attainment was observed across all doses. This LSS for levofloxacin can be used for therapeutic drug monitoring and for future pharmacokinetic/pharmacodynamic studies.
Details
- Title: Subtitle
- Limited sampling strategy and target attainment analysis for levofloxacin in patients with tuberculosis
- Creators
- Abdullah Alsultan - University of Florida, College of Pharmacy, Department of Pharmacotherapy and Translational Research, and the Emerging Pathogens Institute, Gainesville, Florida, USAGuohua An - University of Iowa, College of Pharmacy, Division of Pharmaceutics and Translational Therapeutics, Iowa City, Iowa, USACharles A Peloquin - University of Florida, College of Pharmacy, Department of Pharmacotherapy and Translational Research, and the Emerging Pathogens Institute, Gainesville, Florida, USA peloquin@cop.ufl.edu
- Resource Type
- Journal article
- Publication Details
- Antimicrobial agents and chemotherapy, Vol.59(7), pp.3800-3807
- Publisher
- United States
- DOI
- 10.1128/AAC.00341-15
- PMID
- 25870068
- PMCID
- PMC4468713
- ISSN
- 0066-4804
- eISSN
- 1098-6596
- Grant note
- N01AI95383 / NIAID NIH HHS N01-AI-7022 / NIAID NIH HHS N01-AI95383 / NIAID NIH HHS
- Language
- English
- Date published
- 07/2015
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984065691002771
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