Ranitidine and NDMA: An Overview of Metabolism and Contamination Issues
When it comes to the metabolism of ranitidine, the initial research suggested that it does not convert to NDMA (N-nitrosodimethylamine) in the stomach. However, recent studies have brought up some controversies regarding this issue. Given the conflicting results, it is important to understand the scientific background and current findings.
Understanding the Structure of NDMA
N-nitrosodimethylamine (NDMA) is a nitrosamine compound that has been linked to potential carcinogenic risks in humans. The structure of NDMA is as follows:
Metabolism of Ranitidine
The metabolism of ranitidine has been studied extensively. In unadulterated samples, the primary finding indicates that ranitidine does not convert to NDMA in the stomach. Studies involving the oral administration of ranitidine have shown that unchanged drug is the major component, and compound I is the major metabolite.
A study involving the oral administration of 400 mg of unlabelled ranitidine hydrochloride per day to male volunteers revealed that unchanged drug is the major component, and compound I is the major metabolite. Only small amounts of compounds II and III were present in the human urine collected after administration.
Recent Controversies and Retractions
Despite the initial findings, recent research has brought up some unexpected results. In 2016, a study by Zang and Mitch published in Carcinogenesis found minor quantities of NDMA in the urine of 12 patients. However, in November 2021, this study was retracted. The retraction was due to the identification of an analytical artifact associated with the use of gas chromatography that could have influenced the NDMA measurements in the study. Given this artifact, the authors confirmed that their NDMA measurements were not reliable.
New Findings and Reliable Studies
More recently, a new study has found the opposite of the Zang and Mitch findings. This study did not detect NDMA in the urine of the tested subjects, suggesting that ranitidine does not convert to NDMA in the gastrointestinal (GI) tract under normal circumstances.
Regulatory Concerns and FDA Updates
The U.S. Food and Drug Administration (FDA) has been closely monitoring the issue of NDMA contamination in ranitidine products. While some ranitidine medicines, including Zantac, have been found to contain low levels of NDMA, the FDA and other regulatory bodies continue to investigate and monitor these products.
R1: Some ranitidine medicines, including some products commonly known as the brand-name drug Zantac, contain a nitrosamine impurity called N-nitrosodimethylamine (NDMA) at low levels. Ranitidine is an H2 histamine-2 blocker which decreases the amount of acid created by the stomach.
Conclusion
The initial findings suggested that ranitidine does not convert to NDMA in the stomach, but recent research has challenged this conclusion. However, considering the retraction of the Zang and Mitch paper, the current consensus is that ranitidine does not convert to NDMA under normal circumstances. Nonetheless, regulatory bodies continue to monitor these products to ensure the safety of consumers.