Impact of food and antacids on the pharmacokinetics of anti-tuberculosis drugs: systematic review and meta-analysis

OBJECTIVE: To compare the effects of food and antacids on the bioavailability of first-line anti-tuberculosis drugs. METHOD: Systematic search of electronic databases Pub Med (January 1950-May 2009), and the Cochrane Library database (January 1974-May 2009), including the Cochrane Centre register of controlled trials, and ongoing trials from research registers using key terms 'food', 'antacids', 'meal', 'controlled trial', 'diet', and the first-line anti-tuberculosis drugs isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and pyrazinamide (PZA). Meta-analysis was performed using Rev Man software 5 to assess the impact of food or antacids on the maximum plasma concentrations (C-max) and area under the plasma concentration time curve (AUC) of anti-tuberculosis drugs. RESULTS: Twelve trials involving 157 patients were included in the meta-analysis. The overall effects showed that food significantly reduced the C-max mean difference (C-max MD; C-max MD -1.42, 95% CI -1.56- -1.28, P < 0.00001) and AUC (C-max MD -3.33, 95% CI -4.05- -2.62, P < 0.00001) of INH but antacids did not. Food also significantly reduced the C-max MD (C-max MD -2.47, 95% CI -3.30- -1.64, P < 0.00001) but not the AUC of RMP. Antacids had no effect on the C-max MD or AUC of RMP. The C-max and AUC of PZA were unaffected by both food and antacids. Both food and antacids reduced the C-max but not the AUC of EMB. CONCLUSION: From a pharmacokinetic point of view, it seems that the better option for patients with gastrointestinal upsets during chemotherapy would be to add antacids rather than dosing with meals.