Metz D C, Buchanan M, Purich E, Fein S
Division of Gastroenterology, Hospital of The University of Pennsylvania, University of Pennsylvania Health System, Philadelphia, PA 19107, USA.
Aliment Pharmacol Ther. 2001 May;15(5):669-76. doi: 10.1046/j.1365-2036.2001.00976.x.
Although biologically-derived porcine secretin is approved for the diagnosis of Zollinger-Ellison Syndrome, it is no longer available in the United States. Pure human and porcine secretins have now been synthesized and new drug applications have been filed with the Federal Drug Administration (FDA).
In the current study we compared secretin testing results in six confirmed Zollinger-Ellison Syndrome patients using the biologically-derived product and both synthetic products (human and porcine) in a three-way, randomized, single-blind Latin-squares crossover study.
Using the FDA-approved criterion for positive secretin testing (i.e. a serum gastrin concentration increase of > 110 pg/mL), there was complete agreement between all three agents for all patients. With the more stringent NIH criterion (i.e. a serum gastrin concentration increase of > 200 pg/mL), positive results persisted in five out of six, six out of six and four out of six patients using biologically-derived secretin, synthetic porcine secretin, and synthetic human secretin, respectively (six out of six, six out of six and four out of six if a positive test was defined as a 50% increase in serum gastrin concentration). The time to peak serum gastrin concentration after secretin injection occurred within 15 min in all studies (in 94% by 10 min and in 77% by 5 min). Three-way comparisons of serum gastrin concentrations showed a single statistically significant difference (the change from baseline at 15 min between synthetic human and synthetic porcine secretin, P=0.0274). Statistically significant changes from baseline occurred at 1, 2 and 5 min for biologically-derived porcine secretin and at 2 and 5 min for both synthetic porcine and synthetic human secretin, in keeping with the expected time curve for positive tests. All three agents were well-tolerated.
These data suggest that either synthetic secretin product, when released onto the United States market, can be used to confirm Zollinger-Ellison Syndrome.
尽管生物源猪促胰液素已被批准用于诊断卓-艾综合征，但在美国已不再可用。现在已合成了纯人促胰液素和猪促胰液素，并已向美国食品药品监督管理局（FDA）提交了新药申请。
在本研究中，我们采用三向、随机、单盲拉丁方交叉研究，比较了6例确诊的卓-艾综合征患者使用生物源产品以及两种合成产品（人促胰液素和猪促胰液素）进行促胰液素检测的结果。
采用FDA批准的促胰液素检测阳性标准（即血清胃泌素浓度升高>110 pg/mL），所有三种制剂在所有患者中结果完全一致。采用更严格的美国国立卫生研究院（NIH）标准（即血清胃泌素浓度升高>200 pg/mL），使用生物源促胰液素、合成猪促胰液素和合成人促胰液素时，分别有6例中的5例、6例中的6例和6例中的4例结果为阳性（如果将阳性检测定义为血清胃泌素浓度升高50%，则分别为6例中的6例、6例中的6例和6例中的4例）。在所有研究中，注射促胰液素后血清胃泌素浓度达到峰值的时间均在15分钟内（10分钟时达到的占94%，5分钟时达到的占77%）。血清胃泌素浓度的三向比较显示有一个统计学上的显著差异（合成人促胰液素和合成猪促胰液素在15分钟时相对于基线的变化，P = 0.0274）。生物源猪促胰液素在1、2和5分钟时相对于基线有统计学上的显著变化，合成猪促胰液素和合成人促胰液素在2和5分钟时相对于基线有统计学上的显著变化，这与阳性检测的预期时间曲线一致。所有三种制剂耐受性良好。
这些数据表明，两种合成促胰液素产品在美国上市后，均可用于确诊卓-艾综合征。
