Relative bioavailability of olsalazine from tablets and capsules: A drug targeted for local effect in the colon

The aim of this investigation was to compare two formulations of the prodrug oisaiazine (OLZ) with regard to local bioavailability of 5‐aminosalicylic acid (5‐ASA) in the colon. Since 5‐ASA can not be measured directly in the colon, the bioavailability was evaluated by studying the plasma concentration and cumulative urinary excretion (Ae) of its main metabolite N‐acetyl‐5‐aminosalicylic acid (ac‐5‐ASA). The absorption of OLZ was also studied. A single dose of lg OLZ tablets and capsules was given to nine healthy fasting volunteers in two repeated two‐period cross‐over studies. Blood and urine samples were collected for 72 and 96h, respectively. AUC, Cmax and Ae data from both studies were combined for statistical analysis. Ninety per cent confidence limits for differences in mean AUC for ac‐5‐ASA (tablet‐capsule) compared to that of capsules were ‐0·31 per cent and 30·8 per cent. This indicates bioequivalence if a more relaxed criterion than the conventional ·20 per cent is applied, which is justified in this situation. The 90 per cent confidence limits for Cmax were ‐10·5 per cent and 36·9 per cent while for Ae the values were ‐20·5 per cent and 23·7 per cent. Within and between subject variability estimates for AUC of ac‐5‐ASA were 24 per cent and 46 per cent, respectively.