Abstract:

Objective This study aimed to analyze the plasma concentrations of first-line anti-tuberculosis drugs in tuberculosis patients.Methods A total of 909 patients (909 for isoniazid (INH), 783 for ethambutol (EMB), 587 for pyrazinamide (PZA), and 503 for rifampin (RFP)), who admitted to Beijing Chest Hospital Affilia-ted to Capital Medical University from January 2010 to November 2016 and initiated a daily first-line regimen for treatment of tuberculosis, were selected as the subjects of this study. The doses of medicine were: INH 300 mg/d; RFP 450 mg/d or 600 mg/d; PZA 1500 mg/d; or EMB 750 mg/d. Basic information including gender, age and comorbidity and concentrations of INH, EMB, PZA and RFP were collected and analyzed.Results 57.3% (521/909, INH), 82.2% (644/783, EMB), 29.8% (175/587, PZA), 51.6% (190/368, RFP 450 mg/d) and 36.3% (49/135, RFP 600 mg/d) cases had a C2h lower than the reference ranges. 67.2% (396/589), 85.9% (451/525), 39.9% (153/383) and 60.0% (135/225) of male patients had a C2h lower than the reference ranges of these drugs (INH, EMB, PZA and RFP 450 mg/d), which were significantly higher than the counterparts of female cases (39.1% (125/320), 74.8% (193/258), 10.8% (22/204) and 38.5% (55/143)). The differences were statistically significant (χ ²=67.26, 14.59, 54.10 and 16.24; Ps<0.01). 61.7% (428/694), 83.3% (513/616), 35.3% (159/451) and 55.6% (154/277) of cases with body weight ≥50 kg had a C2h lower than the reference ranges of drugs (INH, EMB, PZA and RFP 450 mg/d), which were significantly higher than the counterparts of those with body weight <50 kg (30.3% (40/132), 72.4% (76/105), 4.7% (4/86) and 37.1% (23/62)). The differences were statistically significant (χ ²=44.44, 7.12, 32.00 and 6.95; Ps<0.05). Low plasma drug concentration of INH and PZA often occurred in cases with diabetes mellitus, with a proportion of 72.6% (143/197) and 53.8% (71/132), compared with those without diabetes mellitus (53.1% (378/712) and 22.9% (104/455)). The differences were statistically significant (χ ²=23.98 and 46.78; Ps<0.01). Conclusion It is common that tuberculosis patients have low blood drug concentrations after taking first-line anti-tuberculosis drugs. The individual’s situation varies with several factors including gender, body weight and comorbidity. The monitoring of blood concentration of first-line anti-tuberculosis drugs should be carried out, and modification of treatment plans based on individual’s conditions is essential for therapeutic goals.

Key words: Tuberculosis, Drug monitoring, Pharmacokinetics, Rifampin, Isoniazid, Ethambutol, Pyrazinamide