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Current research toward optimizing dosing of first-line antituberculosis treatment
Helen McIlleron1, Maxwell T Chirehwa1
1a Division of Clinical Pharmacology, Department of Medicine , University of Cape Town , Cape Town , South Africa.
Expert Review of Anti-Infective Therapy
|December 4, 2018
Summary
Optimized weight-based dosing for tuberculosis drugs improves drug exposure equity. Addressing pharmacokinetic variability, including genetic factors and drug quality, is crucial for effective tuberculosis treatment globally.
Area of Science:
- Pharmacology
- Infectious Diseases
- Public Health
Background:
- Antituberculosis drug concentrations exhibit significant variability in patients, impacting treatment outcomes.
- Factors contributing to this pharmacokinetic variability include patient characteristics, drug interactions, and product quality.
Purpose of the Study:
- To review literature on factors influencing antituberculosis drug pharmacokinetic variability.
- To propose simplified weight-based dosing strategies for fixed-dose combinations (FDCs) in adults with drug-susceptible tuberculosis.
- To highlight needs for optimized pediatric dosing and quality control of antituberculosis drugs.
Main Methods:
- Literature review of factors affecting pharmacokinetic variability of antituberculosis drugs.
- Application of population pharmacokinetic models using data from African tuberculosis patients.
- Analysis of weight, height, and sex distributions to inform dosing recommendations.
Main Results:
- Proposed simplified weight-band-based dosing for FDCs in adult tuberculosis patients to improve drug exposure equity.
- Identified genetic variants, drug-drug interactions, and formulation quality as key contributors to variability.
- Emphasized the need for optimized pediatric formulations and improved quality assurance for antituberculosis drugs.
Conclusions:
- Optimized weight-band dosing enhances equitable drug exposure distribution.
- Stratified dosing based on acetylator type could improve isoniazid use in drug-resistant tuberculosis.
- Urgent need for improved pediatric formulations and stringent quality control of antituberculosis drugs is highlighted.
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