Limited sampling strategy and target attainment analysis for levofloxacin in patients with tuberculosis
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…
Read the paper
Related studies
- Ferulic acid regulates the AKT/GSK-3β/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model
- Novel Pharmacokinetic/Pharmacodynamic Parameters Quantify the Exposure–Effect Relationship of Levofloxacin against Fluoroquinolone-Resistant Escherichia coli
- Photochemical behavior of levofloxacin
- Correlation Between Dissolution Profiles of Salt-Form Drugs in Biorelevant Bicarbonate Buffer and Oral Drug Absorption: Importance of Dose/ Fluid Volume Ratio
- Evaluation of the synergistic potential and mechanisms of action for de novo designed cationic antimicrobial peptides
- Synthesis of [11C]levofloxacin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.