To evaluate the plasma concentrations of isoniazid in different dosage forms among tuberculosis patients to guide clinical therapy of this infectious disease.

A total of 128 patients who were hospitalized for initial treatment of tuberculosis at the Department of Drug Resistant and Severe Tuberculosis, the Third People′s Hospital of Kunming from May 2016 to June 2017 were randomly divided into either an injection group (n=65) or an oral group (n=63) according to the dosage form of isoniazid. After 7 days of standardized medication, plasma isoniazid concentrations were tested at seven different time points in the two groups. In the injection group, the time points of blood collection were 0, 1, 2, 3, 4, 8, and 24 hours after the completion of isoniazid infusion. In the oral group, the time points were 0.5, 1, 2, 3, 4, 8, and 24 hours after taking isoniazid. The rank sum test was used to compare the differences of blood drug concentration, peak concentration, trough concentration, and mean blood drug concentration between the two groups at different blood sampling points. The chi-square test was used to compare the differences in the number of cases in whom isoniazid reached the minimum inhibitory concentration between the two groups.

For the injection group, the highest concentration of isoniazid occurred immediately after injection, and the concentration was 2.78 (1.86, 4.81) μg/ml; for the oral group, it occurred 2 hours after taking the medicine [1.00 (0.67, 2.54) μg/ml]. Plasma concentrations of isoniazid in the injection group were significantly higher than those of the oral group at the 1st, 2 nd, and 3 rd sampling points [2.78 (1.86, 4.81) μg/ml vs 0.35 (0.04, 2.28) μg/ml; 2.05 (1.41, 2.49) μg/ml vs 0.76 (0.06, 3.03) μg/ml; 1.02 (1.49, 2.22) μg/ml vs 1.00 (0.67, 2.54) μg/ml; Z=-5.354, -3.394, -2.155; P<0.001, P=0.001, P=0.031]. The peak concentration, trough concentration, and mean concentration of isoniazid were higher in the injection group than in the oral group [3.334 (2.187, 5.310) μg/ml vs 1.179 (0.869, 1.754) μg/ml; 0.009 (0.003, 0.056) μg/ml vs 0.003 (0.001, 0.144) μg/ml; 1.179 (0.869, 1.754) μg/ml vs 0.680 (0.431, 1.836) μg/ml]; the peak concentration and mean concentration in the injection group were statistically different from those in the oral group (Z=-4.631, -1.205, -3.414; P<0.001, P=0.228, P=0.001). The percentage of cases who achieved minimum inhibitory concentration (MIC) in the injection group and oral group was 88.5% and 87.8%, respectively, and there was no statistical difference between the two groups (χ²=0.114, P=0.736).

Plasma concentrations of isoniazid in the injection group are higher than those in the oral group. For patients with severe pulmonary tuberculosis, we suggest that injection of isoniazid be used to increase the concentration of plasma and improve the clinical effects.

Isoniazid; Injection; Oral administration; Plasma concentration