口服美沙拉嗪（艾迪莎）和巴柳氮等摩尔剂量5-氨基水杨酸酯的比较药代动力学：一项在健康志愿者中进行的随机、单剂量、交叉研究。

Comparative pharmacokinetics of equimolar doses of 5-aminosalicylate administered as oral mesalamine (Asacol) and balsalazide: a randomized, single-dose, crossover study in healthy volunteers.

作者信息

Sandborn W J, Hanauer S B, Buch A

机构信息

Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

出版信息

Aliment Pharmacol Ther. 2004 May 15;19(10):1089-98. doi: 10.1111/j.1365-2036.2004.01964.x.

DOI:10.1111/j.1365-2036.2004.01964.x

PMID:15142198

Abstract

BACKGROUND

Existing pharmacokinetic data are insufficient to determine whether a delayed-release formulation of mesalamine (Asacol) results in greater systemic exposure to 5-aminosalicylic acid and its major metabolite N-acetyl-5-aminosalicylic acid than a prodrug (balsalazide).

AIM

To determine the pharmacokinetic parameters of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid from equimolar doses of 5-aminosalicylic acid administered as Asacol and balsalazide.

METHODS

Nineteen healthy volunteers completed an open-label, single-dose, randomized, crossover study comparing the pharmacokinetics of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid from equimolar doses of 5-aminosalicylic acid (800 mg) administered as Asacol (800 mg) and balsalazide (2250 mg). Plasma and urine samples were analysed for 5-aminosalicylic acid, N-acetyl-5-aminosalicylic acid, and balsalazide (urine only) using high-performance liquid chromatography methods with mass spectrometric detection. Pharmacokinetic parameters assessed for 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid included: percentage of dose excreted in urine (A(e)%), area under the plasma concentration-time curve (AUCt(last)); and maximum plasma concentration (C(max)).

RESULTS

The geometric mean total (5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid) urinary excretion values (A(e)%) of Asacol and balsalazide were 19.26 and 19.31% (P = 0.98). The geometric mean A(e)% values of 5-aminosalicylic acid for Asacol and balsalazide were 0.39 and 0.37% (P = 0.78); the geometric mean A(e)% values of N-acetyl-5-aminosalicylic acid for Asacol and balsalazide were 18.78 and 18.83% (P = 0.98). The geometric mean 5-aminosalicylic acid AUC(t(last)) values for Asacol and balsalazide were 3295 and 3449 ng h/mL (P = 0.85); the geometric mean N-acetyl-5-aminosalicylic acid AUC(t(last)) values for Asacol and balsalazide were 15 364 and 16 050 ng h/mL (P = 0.69). The geometric mean 5-5-aminosalicylic acid C(max) values for Asacol and balsalazide were 319 and 348 ng/mL (P = 0.80); the geometric mean N-acetyl-5-aminosalicylic acid C(max) values for Asacol and balsalazide 927 and 1009 ng/mL (P = 0.67).

CONCLUSIONS

The systemic absorption of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid from Asacol and balsalazide are comparable based upon plasma pharmacokinetic parameters and urinary excretion values.

摘要

背景

现有的药代动力学数据不足以确定美沙拉嗪（艾迪莎）的缓释制剂是否比前体药物（巴柳氮）导致5-氨基水杨酸及其主要代谢物N-乙酰-5-氨基水杨酸有更高的全身暴露量。

目的

确定以艾迪莎和巴柳氮形式给予等摩尔剂量的5-氨基水杨酸后，5-氨基水杨酸和N-乙酰-5-氨基水杨酸的药代动力学参数。

方法

19名健康志愿者完成了一项开放标签、单剂量、随机、交叉研究，比较了以艾迪莎（800mg）和巴柳氮（2250mg）形式给予等摩尔剂量的5-氨基水杨酸（800mg）后5-氨基水杨酸和N-乙酰-5-氨基水杨酸的药代动力学。使用带质谱检测的高效液相色谱法分析血浆和尿液样本中的5-氨基水杨酸、N-乙酰-5-氨基水杨酸和巴柳氮（仅尿液）。评估5-氨基水杨酸和N-乙酰-5-氨基水杨酸的药代动力学参数包括：尿中排泄剂量百分比（A(e)%）、血浆浓度-时间曲线下面积（AUCt(last)）；以及最大血浆浓度（C(max)）。

结果

艾迪莎和巴柳氮的几何平均总（5-氨基水杨酸和N-乙酰-5-氨基水杨酸）尿排泄值（A(e)%）分别为19.26%和19.31%（P = 0.98）。艾迪莎和巴柳氮的5-氨基水杨酸的几何平均A(e)%值分别为0.39%和0.37%（P = 0.78）；艾迪莎和巴柳氮的N-乙酰-5-氨基水杨酸的几何平均A(e)%值分别为18.78%和18.8 / 18.83%（P = 0.98）。艾迪莎和巴柳氮的5-氨基水杨酸的几何平均AUC(t(last))值分别为3295和3449 ng h/mL（P = 0.85）；艾迪莎和巴柳氮的N-乙酰-5-氨基水杨酸的几何平均AUC(t(last))值分别为15364和16050 ng h/mL（P = 0.69）。艾迪莎和巴柳氮的5-氨基水杨酸的几何平均C(max)值分别为319和348 ng/mL（P = 0.80）；艾迪莎和巴柳氮的N-乙酰-5-氨基水杨酸的几何平均C(max)值分别为927和1009 ng/mL（P = 0.67）。