A new isoniazid preparation designed for moderately fast and "fast" metabolizers of the drug.

The bioavailability of a new isoniazid preparation consisting of 37% ordinary isoniazid (INH) and 63% matrix component was investigated in 11 slow, 8 moderately fast, and 9 "fast" acetylators of the drug. Initially, a 15 mg/kg dose of normal INH was administered to all the participants. In addition, the two groups of fast metabolizers received 30 and 45 mg INH-matrix/kg, respectively, with a one-week interval between the test doses. These high dosages of the INH-matrix could be given without encountering toxic reactions because of the delayed absorption of the matrix formulation. In moderately fast acetylators, with a triple dose of matrix isoniazid, it was possible to mimic the blood levels produced by 15 mg ordinary INH/kg in slow inactivators. However, in "fast" acetylators the blood concentrations achieved with the 45 mg/kg dose of INH-matrix were somewhat lower. This study also showed that a large input rate is essential to procure the required, high blood levels in fast metabolizers. The therapeutic implications of the results of this bioavailability trial are discussed.