Pharmacokinetics of isoniazid under fasting conditions, with food, and with antacids
Abstract:STUDY OBJECTIVES: To determine the intra- and intersubject variability in and the effects of food or antacids on the pharmacokinetics of isoniazid (INH).
DESIGN: Randomized, four-period cross-over Phase I study in 14 healthy male and female volunteers. Subjects ingested single doses of INH 300 mg under fasting conditions twice, with a high-fat meal, and with aluminum-magnesium antacid. They also received standard doses of rifampin, pyrazinamide, and ethambutol.
RESULTS: Serum was collected for 48 hours, and assayed by high performance liquid chromatography (HPLC). Data were analyzed using noncompartmental methods and a compartmental analysis using nonparametric expectation maximization. Both fasting conditions produced similar results: a mean INH Cmax of 5.53 ± 2.92 μg/ml, Tmax of 1.02 ± 1.10 hours, and AUC0-∞ of 20.16 ± 12.45 μg * hr/ml. These findings are similar to those reported previously. Antacids did not alter these parameters significantly (Cmax of 5.62 ± 2.53 μg/ml, Tmax of 0.71 ± 0.56 hours, and AUC0-∞ of 20.27 ± 11.39 μg*hr/ml). In contrast, the high-fat meal recommended by the Food and Drug Administration reduced INH Cmax by 51% (2.73 ± 1.70 μg/ml), nearly doubled Tmax (1.93 ± 1.61 hours), and reduced AUC0-∞ by 12% (17.72 ± 10.32 μg* hr/ml).
CONCLUSIONS: These changes in Cmax, Tmax, and AUC0-∞ can be avoided by giving INH on an empty stomach whenever possible.
Document Type: Regular Paper
Publication date: 1999-08-01
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