Table 3. . Pharmacokinetic sampling sites.

Sampling site	Advantages	Disadvantages
Peripheral blood (plasma or serum)	Ease of repeat sampling Multiple/rich PK sampling possible Most existing data for comparison are from these samples	Far from site of infection Unclear relationship with outcome Wide interindividual variability
Bronchoalveolar lavage	‘Near infection’ samples - alveolar macrophages and epithelial lining fluid Can be paired with rich plasma/serum sampling Models of intrapulmonary exposure can be developed using population modeling techniques	Invasive procedure Single time point sampling Sample from alveoli and bronchioles rather than within granuloma Drug loss due to efflux when sampling Differential penetration depending on inflamed/noninflamed lung/different lobes Sampling retrieves mixture of macrophages, T-lymphocytes and epithelial cells
Lung explant studies	Can assess spatial drug penetration Can combine with spatial data on drug susceptibility profile and MIC	Only possible in patients requiring lung resection (either severe disease or a sub-set of MDR-TB patients) Single time point drug concentrations
Cerebrospinal fluid (for TB meningitis)	Accessible Can be paired with rich plasma sampling Models of CSF drug exposure can be developed using population modeling techniques	Invasive procedure Single time point sampling Traumatic tap will contaminate samples

CSF: Cerebrospinal fluid; MDR: Multidrug resistant; MIC: Minimum inhibitory concentration.