Pharmacokinetics of para-aminosalicylic acid granules under four dosing conditions.
OBJECTIVE
To determine the pharmacokinetics and relative bioavailability of para-aminosalicylic acid (PAS) granules.


METHODS
Phase I pharmacokinetics study.


METHODS
University of Arizona School of Pharmacy.


METHODS
Sixteen healthy male and female volunteers aged 36 +/- 8 years.


METHODS
Subjects received single doses of PAS granules (6 g) combined with cycloserine 500 mg, clofazimine 200 mg, ethionamide 500 mg, and pyridoxine 100 mg. Drugs were given on an empty stomach after an overnight fast (reference) with high-fat food, with orange juice, and with antacids.


RESULTS
Four subjects did not complete all four treatments due to adverse events or personal reasons. Plasma and urine samples were collected for 48 hours and measured by a validated HPLC assay. Pharmacokinetic data analysis was performed with WinNonlin using noncompartmental methods and a one-compartmental model. Bioequivalence testing was performed using the mean ratios of the maximum concentrations (Cmax) and AUC(0-infinity) of PAS, with 90% confidence intervals. Compared with the fasted condition, food increased Cmax 1.5-fold and AUC(0-infinity) 1.7-fold, and it doubled the time to maximum concentration (tmax). The least-squares mean ratios (treatment/reference) for Cmax 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 antacid treatment, respectively. Corresponding ratios for AUC(0-infinity) were 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 orange juice and antacids had minor effects.
Peloquin
C A
CA
Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206-2762, USA. peloquinc@njc.org
Zhu
M
M
Adam
R D
RD
Singleton
M D
MD
Nix
D E
DE
D000328:Adult; D010131:Aminosalicylic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000863:Antacids / Q000494:pharmacology; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001628:Beverages; D002957:Citrus; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000494:pharmacology; D004311:Double-Blind Method; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D008297:Male; D011208:Powders; D013810:Therapeutic Equivalency
D000863:Antacids; D000995:Antitubercular Agents; D004041:Dietary Fats; D004338:Drug Combinations; D011208:Powders; D010131:Aminosalicylic Acid