A prospective study was conducted to recruit patients diagnosed with pulmonary tuberculosis from the Inpatient Department of the Wenzhou Central Hospital from October 1, 2015 to January 31, 2016. A total of 72 patients were enrolled. Subjects were initially treated or retreated once, and both bacteriologically confirmed and clinically diagnosed cases were eligible. Plasma samples were collected 0.5h before and 2h, 4h, 6h, 8h after taking standard quadruple drugs for one week doses. Plasma concentrations were determined using LC-MS/MS. Patients were followed up 2 months after the initiation of treatment to assess the relationships between sputum negative conversion and plasma concentrations.

Among the 72 patients, one patient was confirmed to have multidrug-resistant tuberculosis and one patient was lost to follow up. Thus, 70 patients were analyzed at last, among whom 16 patients were bacteriologically negative and 54 patients were bacteriologically positive at initial diagnosis. The plasma exposures at steady state after one week of drug administration were analyzed. 25.7% (18/70) patients had a plasma peak concentration (C_max) of rifampicin lower than the recommended range (<8μg/ml), 38.6% (27/70) cases had a C_max of isoniazid lower than the recommended range (<3μg/ml), whereas 65.7% (46/70) patients had a C_max of ethambutol lower than the recommended range (<2μg/ml). After 2-month of treatment, among the 54 patients who were sputum bacteria positive at initial diagnosis, 48 patients conversed to sputum bacteria negative, while sputum bacteria were still detected in 6 patients. The C_2h, C_max, and AUC_0-8 of ethambutol were significantly higher in patients who got sputum conversion after 2-month of treatment ((1.81±0.91)μg/ml, (1.81±0.85)μg/ml, and (7.67±3.25)μg·h·ml ^-1) compared with those who failed to get sputum conversion ((0.93±0.32)μg/ml, (1.06±0.25)μg/ml, and (4.93±0.72)μg·h·ml ^-1) (t=4.74, P<0.01; t=4.93, P<0.01; and t=4.95, P<0.01, respectively). The C_2h and C_max of isoniazid were significantly higher in patients who got sputum conversion after 2-month of treatment ((3.67±1.64)μg/ml and (3.85±1.59)μg/ml) compared with those who failed to get sputum conversion ((2.11±1.14)μg/ml and (2.11±1.14)μg/ml) (t=2.60, P=0.012; t=2.25, P=0.029, respectively).

The C_max of drugs below the recommended reference ranges, especially isoniazid and ethambutol, were observed in some patients with pulmonary tuberculosis. The dosage of isoniazid and ethambutol may need to be modified. In addition, the sputum negative conversion after 2-month of treatment was shown to be related with the serum concentration of isoniazid and ethambutol.