Single Saliva Sample Model-Informed Precision Dosing of Levofloxacin for Multidrug-Resistant Tuberculosis

Area of Science:

• Pharmacokinetics
• Tuberculosis Treatment
• Drug Monitoring

Background:

• Levofloxacin is crucial for multidrug-resistant tuberculosis (MDR-TB) but has high pharmacokinetic variability.
• Optimizing levofloxacin exposure through therapeutic drug monitoring (TDM) is vital for treatment success.
• Traditional TDM relies on invasive blood sampling, posing feasibility challenges.

Purpose of the Study:

• To develop a population pharmacokinetic (popPK) model for levofloxacin using both plasma and saliva data.
• To assess the utility of saliva-based limited sampling strategies for levofloxacin TDM.
• To support model-informed TDM for levofloxacin in clinical practice.

Main Methods:

• Collected paired plasma and saliva samples from adult patients receiving oral levofloxacin.
• Developed a plasma-and-saliva popPK model using NONMEM, including covariate analysis.
• Evaluated saliva sampling strategies for predicting plasma area under the curve (AUC24) using Bayesian estimation and simulations.

Main Results:

• A one-compartment model with a saliva bio-compartment accurately described levofloxacin pharmacokinetics.
• Saliva-based sampling strategies, including a single 2-hour sample, accurately predicted plasma AUC24 within acceptable limits.
• No significant covariates impacting levofloxacin pharmacokinetics were identified.

Conclusions:

• The developed popPK model allows reliable levofloxacin exposure estimation from limited saliva samples.
• A single 2-hour post-dose saliva sample can support model-informed levofloxacin TDM in MDR-TB care.
• This non-invasive approach enhances TDM feasibility, especially where blood sampling is challenging.