Poor response to tuberculosis (TB) therapy might be attributable to subtherapeutic levels in drug-compliant patients. Pharmacokinetic\n(PK) parameters can be affected by several factors, such as comorbidities or the interaction of TB drugs with food. This\nstudy aimed to determine the PK of isoniazid (INH) in a Peruvian TB population under observed daily and twice-weekly (i.e.,\nbiweekly) therapy. Isoniazid levels were analyzed at 2 and 6 h after drug intake using liquid chromatography mass spectrometric\nmethods. A total of 107 recruited patients had available PK data; of these 107 patients, 42.1% received biweekly isoniazid. The\nmean biweekly dose (12.8 mg/kg of body weight/day) was significantly lower than the nominal dose of 15 mg/kg/day (P<0.001),\nand this effect was particularly marked in patients with concurrent diabetes and in males. The median maximum plasma concentration\n(Cmax) and area under the concentration-time curve from 0 to 6 h (AUC0ââ?¬â??6) were 2.77 mg/liter and 9.71 mgÃ?·h/liter,\nrespectively, for daily administration and 8.74 mg/liter and 37.8 mgÃ?·h/liter, respectively, for biweekly administration. There were\nno differences in the Cmax with respect to gender, diabetes mellitus (DM) status, or HIV status. Food was weakly associated with\nlower levels of isoniazid during the continuation phase. Overall, 34% of patients during the intensive phase and 33.3% during\nthe continuation phase did not reach the Cmax reference value. However, low levels of INH were not associated with poorer clinical\noutcomes. In our population, INH exposure was affected by weight-adjusted dose and by food, but comorbidities did not indicate\nany effect on PK. We were unable to demonstrate a clear relationship between the Cmax and treatment outcome in this\ndata set. Twice-weekly weight-adjusted dosing of INH appears to be quite robust with respect to important potentially influential\npatient factors under program conditions.
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