Therapeutic drug monitoring of isoniazid and rifampicin during anti-tuberculosis treatment in Auckland, New Zealand.
There is uncertainty as to the optimal therapeutic concentrations of anti-tuberculosis drugs to achieve cure.



To characterise the use of therapeutic drug monitoring (TDM), and identify risk factors and outcomes for those with concentrations below the drug interval.



Patients treated for tuberculosis (TB) who had rifampicin (RMP) or isoniazid (INH) concentrations measured between 1 January 2005 and 31 December 2012 were studied retrospectively. Matched concentrations and drug dosing time were assessed according to contemporary regional drug intervals (RMP > 6 μmol/l, INH > 7.5 μmol/l) and current international recommendations (RMP > 10 μmol/l, INH > 22 μmol/l). Outcomes were assessed using World Health Organization criteria.



Of 865 patients, 121 had concentrations of either or both medications. RMP concentrations were within the regional drug intervals in 106/114 (93%) and INH in 91/100 (91%). Concentrations were within international drug intervals for RMP in 76/114 (67%) and INH in 53/100 (53%). Low weight-based dose was the only statistically significant risk factor for concentrations below the drug interval. Of the 35 patients with low concentrations, 21 were cured, 9 completed treatment and 5 transferred out. There were no relapses during follow-up (mean 66.5 months).



There were no clinically useful characteristics to guide use of TDM. Many patients had concentrations below international therapeutic intervals, but were successfully treated.
Department of Respiratory Medicine, Auckland District Health Board, Auckland, New Zealand; Centre for International Health, University of Otago, Dunedin, New Zealand.
M J
MJ
Maze
Department of Respiratory Medicine, Auckland District Health Board, Auckland, New Zealand.
J
J
Paynter
Department of Chemical Pathology, LabPlus Laboratories, Auckland, New Zealand.
W
W
Chiu
Research Office, Auckland District Health Board, Auckland, New Zealand.
R
R
Hu
Department of Respiratory Medicine, Auckland District Health Board, Auckland, New Zealand; Department of Infectious Diseases, Auckland District Health Board, Auckland, New Zealand.
M
M
Nisbet
Department of Respiratory Medicine, Auckland District Health Board, Auckland, New Zealand.
C
C
Lewis
D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D016208:Databases, Factual; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D011237:Predictive Value of Tests; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D012293:Rifampin / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D013997:Time Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*
D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin