A Review of Clinical Pharmacokinetic and Pharmacodynamic Relationships and Clinical Implications for Drugs Used to Treat Multi-drug Resistant Tuberculosis

Abstract

Multidrug-resistant tuberculosis (MDR-TB) is becoming a global health crisis. The World Health Organization has released new guidelines for the use of tuberculosis-active drugs for the treatment of patients with MDR-TB. Despite documented activity against tuberculosis isolates, doses and exposure targets are yet to be optimized. Our objective was therefore to review the clinical pharmacokinetic and pharmacodynamic literature pertaining to drugs recommended to treat MDR-TB and to identify target areas for future research. To date, published research is limited but studies were identified that evaluated the pharmacokinetics and pharmacodynamics of these drugs. Exposure targets were assessed and summarized for each drug. Exposure-based targets (e.g., area under the concentration curve/minimum inhibitory concentration) appear to be most commonly associated with predicting drug efficacy. Dose variation studies based on these targets were largely inconclusive. Future research should focus on determining the risks and benefits of dose optimization to meet exposure targets and improve patient outcomes. The role of therapeutic drug monitoring also remains yet to be confirmed, both from a clinical perspective as well as a resource allocation perspective in regions where MDR-TB is active.