Pharmacokinetics of rifampin under fasting conditions, with food, and with antacids

Study objectives: Determine the intrasubject and intersubject variability in, and the effects of food or antacids on, the pharmacokinetics of rifampin (RIF). Design: Randomized, four-period crossover phase I study. Subjects: Fourteen healthy male and female volunteers. Interventions: Subjects ingested single doses of RIF, 600 mg, under fasting conditions twice, with a high-fat meal, and with aluminum-magnesium antacid. They also received standard doses of isoniazid, pyrazinamide, and ethambutol. Measurements and main results: Serum was collected for 48 h and assayed by high-pressure liquid chromatography. Data were analyzed using noncompartmental methods and a compartmental analysis using nonparametric expectation maximization. Both fasting conditions produced similar results: a mean RIF maximal serum concentration (Cmax) of 10.54 ± 3.18 μg/mL, the time at which it occurred (Truax) of 2.42 ± 1.32 h, and the area under the curve from time zero to infinity (AUC(0-∞)) of 57.15 ± 13.41 μg · h/mL. These findings are similar to those reported previously. Antacids did not alter these parameters (Cmax of 10.89 ± 5.22 μg/mL, Tmax of 2.36 ± 1.28 h, and AUC(0-∞) of 58.37 ± 18.49 μg · h/mL). In contrast, the Food and Drug Administration high-fat meal reduced RIF Cmax by 36% (7.27 ± 2.29 μg/mL), nearly doubled Tmax (4.43 ± 1.09 h), but reduced AUC(0-∞) by only 6% (55.20 ± 14.48 μg · h/mL). Conclusions: These changes in Cmax, Tmax, and AUC(0- ∞) can be avoided by giving RIF on an empty stomach whenever possible.