WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Isoniazid is the most widely used first line antituberculosis drug.• It is considered safe during lactation, but limited data are available on the transfer of isoniazid from circulation to milk in lactating women, which can provide an assessment of extent of exposure to the nursling. WHAT THIS STUDY ADDS• The study documents the transfer pattern and milk to plasma (M : P) ratio of isoniazid at a steady state.• Peak plasma and milk concentrations of isoniazid were reached within 1 h and the projected exposure of the drug to the infant is much lower than the prophylactic dose, supporting its safety during breast feeding. AIMTo determine milk to plasma (M : P) ratios and infant dose (absolute and relative) for isoniazid in lactating women on antituberculosis therapy. METHODSConcentrations of isoniazid in plasma and milk were measured in exclusively breast feeding women taking 300 mg day -1 as treatment for tuberculosis. RESULTSPeak plasma and milk concentrations of isoniazid were observed at 1 h. A mean M : PAUC value of 0.89 (95% CI 0.7, 1.1) was calculated for isoniazid from seven women over 24 h. The mean absolute infant dose was estimated to be 89.9 mg kg day -1 (95% CI 65.6, 114) and the relative infant dose was 1.2% of the weight adjusted maternal dose. CONCLUSIONSThe mean relative dose of isoniazid (1.2%) transmitted to the infant via breast milk is below the 10% notional level of concern. These data suggest that isoniazid therapy is safe during breastfeeding.

The results suggested high variation in the frequencies of NAT2 alleles and genotypes within Indian populations, which influence plasma isoniazid concentrations. Further studies of the relationship between NAT2 genotypes and adverse drug events are required to make genotyping a helpful tool for optimizing the isoniazid therapeutic response and minimizing adverse drug reactions, particularly in countries with a high burden of tuberculosis.