Dried Blood Spot Analysis Combined With Limited Sampling Models Can Advance Therapeutic Drug Monitoring of Tuberculosis Drugs

To the Editor—Shrivastava and colleagues propose pharmacokinetic (PK) variability as a working hypothesis for the emergence of multidrug-resistant (MDR) tuberculosis [1]. They used Monte Carlo simulations to demonstrate that between-patient PK variability will result in monotherapy in a relevant proportion of patients in the initial phase of tuberculosis treatment. This inevitably would lead to drug resistance. After confirmation of this hypothesis by evaluation in a clinical setting, it should lead to optimized dosing for specific populations and, if resources are available, even for individuals. The results of the study are important because they associate PK variability with outcome. In the accompanying editorial by Dartois, therapeutic drug monitoring (TDM) is suggested as a tool to monitor PK variability and individualize dose regimens [2]. The limitations of dosage individualization based on pharmacodynamics (PDs) and PKs are thoroughly discussed. The PDs may differ because drug susceptibility may vary geographically and also within patients because subpopulations of Mycobacterium tuberculosis may develop in lesions. The PK assessment may be inadequate because of differences in time to reach maximum plasma concentration (not representative peak levels). These factors have to be taken into account when TDM is performed.