Absorption kinetics of 5-aminosalicylic acid in rat: influence of indomethacin-induced gastrointestinal lesions and Escherichia Coli Nissle 1917 medication.

ABSTRACT

OBJECTIVES: The therapeutic effect of probiotics has been studied in many clinical and experimental studies but no data exist concerning the influence of probiotics on pharmacokinetics of contemporary administered drugs. In this paper, we describe the influence of indomethacin-induced gastrointestinal lesions and Escherichia Coli Nissle 1917 medication on absorption of 5-aminosalicylic acid and its metabolite N-acetyl-5-aminosalicylic acid in rat. METHODS: 5-aminosalicylic acid (5-ASA) was given orally to rat using gastric probe as a suspension (25 mg/kg). The plasma time profiles of 5-ASA and its metabolite were compared between Group A (animals medicated with a suspension of Escherichia coli Nissle 1917 [EcN] in dose of 5 × 108 CFUs/day for 14 consecutive days), Group B (animals with indomethacin [IND]-induced gastrointestinal lesions; single dose of 25 mg/kg of IND), Group C (simultaneous administration of EcN and IND), and Group D (control animals without any medication). The blood samples for HPLC analysis has been taken from incannulated vena jugularis in time 30, 60, 90, 120, 180, 240, 360 min after 5-ASA administration to rat. RESULTS: The pharmacokinetics of 5-ASA was not significantly changed by EcN medication (Group A) in comparison to control animals (Group D). The significantly elevated absorption (AUC and cmax) of 5-ASA was found in animals with induced gastro-enteropathy with concurrently medicated with EcN (Group C) when compred to controls. In the case of metabolite N-acetyl-5-ASA, statistically no-significant differences were found between groups. CONCLUSIONS: Simultaneous probiotics (EcN) medication did not affect absorption 5-ASA from intestinal tract (the main site of ASAs action).