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Int J Tuberc Lung Dis. 1999 Aug;3(8):703-10.

Pharmacokinetics of isoniazid under fasting conditions, with food, and with antacids.

Author information

1
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA. peloquinc@njc.org

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 microg/ml, Tmax of 1.02 +/- 1.10 hours, and AUC0-infinity of 20.16 +/- 12.45 microg x hr/ml. These findings are similar to those reported previously. Antacids did not alter these parameters significantly (Cmax of 5.62 +/- 2.53 microg/ml, Tmax of 0.71 +/- 0.56 hours, and AUC0-infinity of 20.27 +/- 11.39 microg x hr/ml). In contrast, the high-fat meal recommended by the Food and Drug Administration reduced INH Cmax by 51% (2.73 +/- 1.70 microg/ml), nearly doubled Tmax (1.93 +/- 1.61 hours), and reduced AUC0-infinity by 12% (17.72 +/- 10.32 microg x hr/ml).

CONCLUSIONS:

These changes in Cmax, Tmax, and AUC0-infinity can be avoided by giving INH on an empty stomach whenever possible.

PMID:
10460103
[Indexed for MEDLINE]

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