Isoniazid pharmacokinetic studies of the 1960s: considering a higher isoniazid dose in childhood tuberculosis

Abstract

Isoniazid (INH) is one of the most important drugs for the treatment of tuberculosis (TB). In the current international recommendations there is still disagreement on the optimal dosage of INH in childhood TB. This paper presents data from 2 studies, one performed in 1960 and the other in 1961, investigating INH serum levels in children of different age groups, not yet presented internationally. Doses were calculated according to bodyweight (BW) as well as according to body surface area (BSA). In the first study, INH serum levels at different time points in children of different age groups were determined after oral INH administration at 5 mg/kg BW. In the second study, INH serum levels were measured once, 4 h after subcutaneous application of 5 mg/kg BW and once, 4 h after subcutaneous application of INH 200 mg/m² BSA 1 week later. These data was compared to adult data on INH collected prior to these studies. After application of 5 mg/kg BW oral dose, INH serum levels were much lower in children than in adults at all time points, especially in children younger than 8 y. In contrast, after dosing according to 200 mg/m² BSA, similar serum levels were achieved in children and adults. Dose recommendations of INH 5 mg/kg BW in childhood TB lead to lower serum concentrations than those recommended for adults. In children, it appears to be more appropriate to calculate the INH dose on the basis of body surface area rather than bodyweight.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.