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Clinical Investigations: TUBERCULOSIS |

Pharmacokinetics of Rifampin Under Fasting Conditions, With Food, and With Antacids*

Charles A. Peloquin, PharmD; Rocsanna Namdar, PharmD; Michael D. Singleton, BS; David E. Nix, PharmD
Author and Funding Information

*From the Department of Medicine (Drs. Peloquin and Namdar and Mr. Singleton), National Jewish Medical and Research Center, Denver, CO; School of Pharmacy (Dr. Peloquin) and School of Medicine (Dr. Peloquin), University of Colorado Denver; and School of Pharmacy (Dr. Nix), University of Arizona, Tucson, AZ.



Chest. 1999;115(1):12-18. doi:10.1378/chest.115.1.12
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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 (Tmax) of 2.42 ± 1.32 h, and the area under the curve from time zero to infinity (AUC0–∞) 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 AUC0–∞ of 58.37 ± 18.49μ g · 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 AUC0–∞ by only 6% (55.20 ± 14.48 μg · h/mL).

Conclusions: These changes in Cmax, Tmax, and AUC0–∞ can be avoided by giving RIF on an empty stomach whenever possible.

Abbreviations: ANOVA = analysis of variance; AUC = area under the curve; AUC0–∞ = area under curve from time zero to infinity; C = clearance; CI = confidence interval; ClCr = creatine clearance; Clr = renal clearance; Cmax = maximal serum concentration; CV = coefficient of variation; EMB = ethambutol; HPLC = high-pressure liquid chromatography; INH = isoniazid; K = elimination rate constant; ka = absorption rate constant; MIC = minimal inhibitory concentration; NPEM = nonparametric expectation maximization; PZA = pyrazinamide; QC = quality control; RIF = rifampin; Tmax = time at which maximal serum concentration occurred; V = volume of distribution

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