Studies of serial plasma Isoniazid concentrations with different doses of a slow-release preparation of Isoniazid

The suitability of a slow-release matrix preparation of isoniazid for use in once-weekly chemotherapy has been investigated in South Indian patients. Serial plasma isoniazid concentrations were determined up to 6 hours following doses of 15, 30, 45 and 60 mg/kg body-weight in rapid inactivators and up to 10 hours following doses of 15, 30 and 45 mg/kg in slow inactivators. The isoniazid levels were sustained, and the peak concentrations (per unit dose) were considerably lower than with ordinary isoniazid. It was estimated that a matrix isoniazid dose of 35 mg/kg in slow inactivators and 50 mg/kg in rapid inactivators would produce a peak similar to that attained with a non-toxic dose or ordinary isoniazid 15 mg/kg in slow inactivators. A second investigation showed that matrix isoniazid 40 mg/kg in rapid inactivators produced a coverage (with 0.2 mug/ml) and exposure similar to those attained in slow inactivators with a highly effective dose of ordinary isoniazid 15 mg/kg, while 30 mg/kg gave substantially lower values. In both investigations, disproportionately large increases in plasma isoniazid concentrations were observed in rapid inactivators with an increase in the matrix isoniazid dose. In slow inactivators, both doses of matrix isoniazid, 30 and 40 mg/gk, resulted in coverage and exposure that were substantially higher than those obtained with ordinary isoniazid 15 mg/kg.