Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China.
Institute of Clinical Pharmacy, Central South University, Changsha, China.
Clin Pharmacol Drug Dev. 2020 Jan;9(1):41-49. doi: 10.1002/cpdd.696. Epub 2019 May 6.
This study aimed to simultaneously determine mesalazine (5-ASA) and its major metabolite N-Ac-5-ASA in the plasma and to evaluate the impact of different food patterns on the relative bioavailability and pharmacokinetics of a single oral dose of 5-ASA in healthy subjects. In this single-dose, open-label, 3-period, 3-treatment crossover study, the subjects received a single, oral dose of 500-mg enteric-coated mesalazine tablet together with either a low-fat or a high-fat breakfast or under fasting condition (reference). The pharmacokinetic parameters were determined by noncompartmental methods and analyzed with a linear mixed-effect model. The geometric least squares mean ratio for the area under the plasma concentration-time curve from zero to infinity of N-Ac-5-ASA was 1.05 (90% confidence interval [CI], 0.70-1.58) for high-fat/fasted condition and 1.06 (90%CI, 0.82-1.36) for low-fat/fasted condition. The least squares mean ratio of 5-ASA was 0.86 (90%CI, 0.65-1.14) for high-fat/fasted condition and 0.78 (90%CI, 0.60-1.02) for low-fat/fasted condition. All P values were >.05. The mean maximum plasma concentration and the time to reach the maximum plasma concentration of N-Ac-5-ASA were 2084 ng/mL, 8 hours; 2639 ng/mL, 11 hours, and 2409 ng/mL, 9 hours for fasted, high-fat, and low-fat, respectively. The values of 5-ASA were 1950 ng/mL, 7 hours; 2869 ng/mL, 9 hours; and 2837 ng/mL, 8 hours for fasted, high-fat, and low-fat condition. 5-ASA was well tolerated under all 3 conditions. Food delayed the absorption of 5-ASA, especially a high-fat meal. Therefore, enteric-coated mesalazine tablets should be taken before meals to avoid causing patients slow response and any effect of food on its efficacy.
这项研究旨在同时测定血浆中的美沙拉嗪（5-ASA）及其主要代谢物 N-Ac-5-ASA，并评估不同食物模式对健康受试者单次口服 5-ASA 相对生物利用度和药代动力学的影响。在这项单剂量、开放标签、3 期、3 处理交叉研究中，受试者接受了单次口服 500mg 肠溶片美沙拉嗪，同时给予低脂或高脂肪早餐，或空腹（参考）。药代动力学参数采用非房室模型法测定，并采用线性混合效应模型进行分析。N-Ac-5-ASA 从 0 到无穷大的血浆浓度-时间曲线下面积的几何均数比值分别为高脂肪/禁食条件下的 1.05（90%置信区间[CI]，0.70-1.58）和低脂/禁食条件下的 1.06（90%CI，0.82-1.36）。5-ASA 的最小二乘均值比分别为高脂肪/禁食条件下的 0.86（90%CI，0.65-1.14）和低脂/禁食条件下的 0.78（90%CI，0.60-1.02）。所有 P 值均>0.05。N-Ac-5-ASA 的最大血浆浓度和达到最大血浆浓度的时间的平均值分别为禁食、高脂肪、低脂条件下的 2084ng/mL，8 小时；2639ng/mL，11 小时；2409ng/mL，9 小时。5-ASA 的值分别为禁食、高脂肪、低脂条件下的 1950ng/mL，7 小时；2869ng/mL，9 小时；2837ng/mL，8 小时。所有条件下的 5-ASA 均具有良好的耐受性。食物延迟了 5-ASA 的吸收，尤其是高脂肪餐。因此，肠溶片美沙拉嗪应在饭前服用，以避免引起患者反应迟缓，以及食物对其疗效的任何影响。
