Gionchetti P, Campieri M, Belluzzi A, Boschi S, Brignola C, Miglioli M, Barbara L
Clinica Medica e Gastroenterologia, Policlinico S. Orsola, Università di Bologna, Italy.
Aliment Pharmacol Ther. 1994 Oct;8(5):535-40. doi: 10.1111/j.1365-2036.1994.tb00327.x.
An oral multiparticulate coated formulation of 5-aminosalicylic acid (5-ASA: mesalazine) has been developed to provide a controlled release of the drug, in a pH-dependent fashion, in the distal ileum and colon. The purpose of the present study was to assess the systemic availability of the drug and its metabolite, acetyl-5-ASA, following single (800 mg) and multiple (2400 mg for 56 days) oral dose administration.
Three groups were investigated: six healthy volunteers, six patients with ulcerative colitis, and nine patients with Crohn's disease in remission. In the single oral dose study (800 mg) all three groups participated, whereas in the multiple oral dose study (2400 mg/day for 56 days) only the patients with inflammatory bowel disease took part. Plasma and urine 5-ASA and Ac-5-ASA were measured for 48 h.
In the single oral dose regimen, systemic absorption of 5-ASA and Ac-5-ASA were low and did not differ between the three groups. Only about 20% of the 5-ASA given was absorbed, with more than 80% of the drug being available in the terminal ileum and colon for therapeutic activity. The multiple oral dose regimen in patients with inflammatory bowel disease produced a significantly higher plasma concentration and urine excretion of both 5-ASA and Ac-5-ASA by the end of the treatment, in comparison to the first dose. There was a statistically higher systemic absorption of 5-ASA in patients with ulcerative colitis than in patients with Crohn's disease. After 56 days of dosing, no adverse event was reported and laboratory screening tests remained within normal ranges.
The new oral 5-ASA formulation is gradually released throughout the small and large intestine, reflected by a low plasma concentration of the drug and its metabolite, with about 80% of the drug being available for ileum-colon therapeutic activity.
已研发出一种5-氨基水杨酸（5-ASA：美沙拉嗪）的口服多颗粒包衣制剂，可在回肠末端和结肠以pH依赖方式实现药物的控释。本研究的目的是评估单次（800mg）和多次（2400mg，持续56天）口服给药后该药物及其代谢产物乙酰-5-ASA的全身可用性。
研究了三组对象：6名健康志愿者、6名溃疡性结肠炎患者和9名缓解期克罗恩病患者。单次口服剂量研究（800mg）中所有三组均参与，而多次口服剂量研究（2400mg/天，持续56天）中只有炎症性肠病患者参与。测定48小时内血浆和尿液中的5-ASA和Ac-5-ASA。
在单次口服剂量方案中，5-ASA和Ac-5-ASA的全身吸收较低，三组之间无差异。所给予的5-ASA中只有约20%被吸收，超过80%的药物在回肠末端和结肠可用于治疗活性。与首剂相比，炎症性肠病患者的多次口服剂量方案在治疗结束时使5-ASA和Ac-5-ASA的血浆浓度和尿液排泄均显著升高。溃疡性结肠炎患者的5-ASA全身吸收在统计学上高于克罗恩病患者。给药56天后，未报告不良事件，实验室筛查试验仍在正常范围内。
新的口服5-ASA制剂在整个小肠和大肠中逐渐释放，这表现为药物及其代谢产物的血浆浓度较低，约80%的药物可用于回肠-结肠治疗活性。
