Pharmacokinetics of para-aminosalicylic acid granules under four dosing conditions

SETTING: University of Arizona School of Pharmacy. PARTICIPANTS: Sixteen healthy male and female volunteers aged 36 +/- 8 year s. INTERVENTIONS: Subjects received single doses of PAS granules (6 g) combine d with cycloserine 500 mg, clofazimine 200 mg, ethlonamide 500 mg, and pyri doxine 100 mg. Drugs were given on an empty stomach after an overnight fast (reference) with high-fat food, with orange juice and with antacids. MEASUREMENTS AND RESULTS; Four subjects did not complete all four treatment s due to adverse events or personal reasons. Plasma and urine samples were collected for 48 hours and measured by a validated HPLC assay. Pharmacokine tic data analysis was performed with WinNonlin using noncompartmental metho ds and a one-compartmental model. Bioequivalence testing was performed usin g the mean rations of the maximum concentrations (C-max) and AUC(0 --> infi nity) of PAS, with 90% confidence intervals. Compared with the fasted condi tion, food increased C-max 1.5-fold and AUC(0 --> infinity) 1.7-fold, and i t doubled the time to maximum concentration (t(max)). The least-squares mea n ratios (treatment/reference) for C-max were 0.90 (58% to 139% CI), 1.16 ( 75% to 179% CI) and 0.82 (52% to 127% CI) with orange juice, food, or antac id treatment, respectively. Corresponding ratios for AUC(0 --> infinity) we re 1.05 (71% to 155% CI), 1.52 (103% to 224% CI), and 0.84 (57% to 125% CI) , respectively. CONCLUSIONS: Food significantly enhanced the absorption of PAS, while orang e juice and antacids had minor effects.