美国食品和药物管理局David G. Strauss团队研究了口服雷尼替丁对尿中N-亚硝基二甲胺排泄的影响。2021年6月28日出版的《美国医学会杂志》发表了这项成果。

2019年，美国食品和药物管理局（FDA）收到一份公民请愿书，称雷尼替丁可能含有致癌物质N-亚硝基二甲胺（NDMA）。此外，申诉人提出雷尼替丁可以在人体内转化为NDMA；然而，这主要是基于一项小型临床研究，该研究检测到口服雷尼替丁后尿液中NDMA的排泄增加。

为了比较口服雷尼替丁与安慰剂后24小时尿NDMA排泄情况，2020年6月至7月1日，研究组在美国威斯康星州西本德的临床药理学单位对18名健康受试者进行了一项随机、双盲、安慰剂对照、交叉临床试验。将参与者随机分配到4个治疗队列，在4个疗程内分别接受雷尼替丁和安慰剂，以及非腌肉饮食和腌肉饮食。腌肉饮食设计为含有较高的亚硝酸盐、硝酸盐（硝酸盐还原菌可以将硝酸盐转化为亚硝酸盐）和NDMA。主要结局为24小时尿中NDMA排泄量。

18名随机受试者的中位年龄为33.0岁，9名为女性；7名为白人，11名为非裔美国人；3名为西班牙裔或拉丁裔，共有17名（94%）完成了试验。雷尼替丁和安慰剂组的24小时NDMA尿排泄中位数分别为0.6 ng和10.5 ng，非腌肉饮食组和腌肉饮食组分别为11.9 ng和23.4 ng。雷尼替丁和安慰剂在非腌肉饮食或腌肉饮食的NDMA 24小时尿排泄量方面均没有统计学差异。且均未报告与药物相关的严重不良事件。

总之，在这项包括18名健康受试者的试验中，与安慰剂相比，口服雷尼替丁在受试者食用非腌肉或腌肉饮食时，并未显著增加24小时尿中NDMA的排泄量。研究结果不支持雷尼替丁在一般健康人群中可转化为NDMA。

附：英文原文

Title: Effect of Oral Ranitidine on Urinary Excretion of N-Nitrosodimethylamine (NDMA): A Randomized Clinical Trial

Author: Jeffry Florian, Murali K. Matta, Ryan DePalma, Victoria Gershuny, Vikram Patel, Cheng-Hui Hsiao, Robbert Zusterzeel, Rodney Rouse, Kristin Prentice, Colleen Gosa Nalepinski, Insook Kim, Sojeong Yi, Liang Zhao, Miyoung Yoon, Susan Selaya, David Keire, Joyce Korvick, David G. Strauss

Issue&Volume: 2021-06-28

Abstract:

Importance  In 2019, the US Food and Drug Administration (FDA) received a citizen petition indicating that ranitidine contained the probable human carcinogen N-nitrosodimethylamine (NDMA). In addition, the petitioner proposed that ranitidine could convert to NDMA in humans; however, this was primarily based on a small clinical study that detected an increase in urinary excretion of NDMA after oral ranitidine consumption.

Objective  To evaluate the 24-hour urinary excretion of NDMA after oral administration of ranitidine compared with placebo.

Design, Setting, and Participants  Randomized, double-blind, placebo-controlled, crossover clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) conducted in 18 healthy participants. The study began in June 2020, and the end of participant follow-up was July 1, 2020.

Interventions  Participants were randomized to 1 of 4 treatment sequences and over 4 periods received ranitidine (300 mg) and placebo (randomized order) with a noncured-meats diet and then a cured-meats diet. The cured-meats diet was designed to have higher nitrites, nitrates (nitrate-reducing bacteria can convert nitrates to nitrites), and NDMA.

Main Outcome and Measure  Twenty-four–hour urinary excretion of NDMA.

Results  Among 18 randomized participants (median age, 33.0 [interquartile range {IQR}, 28.3 to 42.8] years; 9 women [50%]; 7 White [39%], 11 African American [61%]; and 3 Hispanic or Latino ethnicity [17%]), 17 (94%) completed the trial. The median 24-hour NDMA urinary excretion values for ranitidine and placebo were 0.6 ng (IQR, 0 to 29.7) and 10.5 ng (IQR, 0 to 17.8), respectively, with a noncured-meats diet and 11.9 ng (IQR, 5.6 to 48.6) and 23.4 ng (IQR, 8.6 to 36.7), respectively, with a cured-meats diet. There was no statistically significant difference between ranitidine and placebo in 24-hour urinary excretion of NDMA with a noncured-meats diet (median of the paired differences, 0 [IQR, 6.9 to 0] ng; P=.54) or a cured-meats diet (median of the paired differences, 1.1 [IQR, 9.1 to 11.5] ng; P=.71). No drug-related serious adverse events were reported.

Conclusions and Relevance  In this trial that included 18 healthy participants, oral ranitidine (300 mg), compared with placebo, did not significantly increase 24-hour urinary excretion of NDMA when participants consumed noncured-meats or cured-meats diets. The findings do not support that ranitidine is converted to NDMA in a general, healthy population.

DOI: 10.1001/jama.2021.9199

Source: https://jamanetwork.com/journals/jama/fullarticle/2781670