Pharmacokinetics of anti-tuberculosis drugs in children.

Tuberculosis (TB) is among the top 10 causes of death among children worldwide. Recent reports suggest that the currently recommended dosages of first-line anti-TB drugs are not adequate in children, particularly younger children. The objective of this review was to synthesize available pharmacokinetic data of anti-TB drugs in children from different settings that would help determine optimal doses of anti-TB drugs, in order to provide evidence-based recommendations. A PubMed database was searched from 1970 to present using the terms rifampicin, isoniazid, pyrazinamide, ethambutol, pharmacokinetics, HIV, TB, nutrition and children. References from identified articles were also reviewed and abstract from recent meetings were included. Available pharmacokinetic data from different settings suggest that age, nutritional status, HIV infection and gene polymorphisms in drug metabolising enzymes could significantly influence the pharmacokinetics of first-line anti-TB drugs. However, most of the pharmacokinetic studies conducted so far in children have failed to associate drug concentrations with treatment outcomes. Hence, more studies to examine the relationship between drug pharmacokinetics and response to anti-TB treatment are required. Studies to examine the impact of nutritional status and HIV infection on the pharmacokinetics of anti-TB drugs in children are needed.