Low serum concentrations of anti-tuberculosis drugs and determinants of their serum levels.
METHODS
Low serum concentrations of anti-tuberculosis drugs have occasionally been associated with treatment failure.


OBJECTIVE
To determine the prevalence of low serum concentrations of anti-tuberculosis drugs and to identify the determinants of drug concentrations.


METHODS
Venous blood was obtained 2 h after drug ingestion, and serum levels of isoniazid (INH), rifampicin (RMP), ethambutol (EMB), pyrazinamide (PZA), acetyl INH and 25-desacetyl RMP were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Patients with human immunodeficiency virus co-infection and gastrointestinal disease or diarrhoea were excluded.


RESULTS
Among 69 enrolled TB patients, the prevalence of a low 2 h serum concentration of at least one anti-tuberculosis drug was 46.4%. Prevalences of a low concentration of INH, RMP, EMB or PZA were 15.2%, 23.5%, 22.4% and 4.5%, respectively. By multivariate linear regression analysis, the serum concentrations of INH, RMP and PZA were positively associated with dose per kg of body weight (P < 0.05). Moreover, INH concentration was associated with acetyl INH/INH ratio (beta = -8.588, P < 0.001) and EMB concentration was associated with calculated creatinine clearance (beta = -0.025, P < 0.001).


CONCLUSIONS
Low concentrations of anti-tuberculosis drugs are common, and although the clinical significance of low concentrations remains uncertain, it may be necessary to optimise drug doses by therapeutic drug monitoring, especially in patients with an inadequate clinical response to chemotherapy.
Um
S-W
SW
Department of Internal Medicine and Lung Institute, Seoul National University College of Medicine, Seoul, South Korea.
Lee
S W
SW
Kwon
S Y
SY
Yoon
H I
HI
Park
K U
KU
Song
J
J
Lee
C-T
CT
Lee
J-H
JH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000097:blood*; D002853:Chromatography, Liquid; D016903:Drug Monitoring; D004977:Ethambutol / Q000097:blood; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000031:analogs & derivatives / Q000097:blood; D016014:Linear Models; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D011718:Pyrazinamide / Q000097:blood; D012293:Rifampin / Q000031:analogs & derivatives / Q000097:blood; D014376:Tuberculosis / Q000097:blood* / Q000188:drug therapy
D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; C510884:acetylisoniazid; C032393:25-deacetylrifampicin; D007538:Isoniazid; D012293:Rifampin