Individualization of antitubercular treatment: evaluation of pharmacological determinants of treatment response

Ilaria Motta

Standardized antitubercular treatment is commonly used but there are still open questions regarding optimal doses, drug exposure and markers of treatment outcome. Relevant findings in pharmacogenomics highlight its potential support to pharmacokinetic (PK) data.
Peripheral blood mononuclear cells (PBMCs) concentrations of anti-TB drugs may be useful for estimating drug distribution as surrogate of alveolar macrophages where metabolic semi-/dormant mycobacteria reside.
The primary aim of this study is to measure plasma and PBMCs drug concentrations, secondary aims are the impact of allelic variants on PK data, the drug concentrations in alveolar macrophages and the association of PK data with microbiological response. A longitudinal observational study will be conducted in Turin in patients with active pulmonary TB. Pharmacokinetic evaluations will be performed at week 1 and 2. Microbiological response at week 2 will be assessed by culture on liquid media and by determination of qPCR of selected micobacterial mRNA. Preliminary pharmacokinetic results show a strong correlation between rifampicin plasma and PBMCs concentrations. The finding of positive association between rifampicin plasma maximum concentrations and TTP warrants to be confirmed. The development of new molecular methods and eventually the association with PK data would permit to detect early failures and preserve the emergence of resistant strains.

Simone Agnello
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