Effect of Oral Ranitidine on Urinary Excretion of N-Nitrosodimethylamine (NDMA): A Randomized Clinical Trial
Trial in 18 healthy subjects found oral ranitidine (300 mg) vs. placebo did not significantly increase 24-hr urinary excretion of NDMA when subjects consumed noncured-meats or cured-meats diets, suggesting ranitidine is not converted to NDMA in a general, healthy population.
Source:
Journal of the American Medical Association
SPS commentary:
In an in vitro study of ranitidine tablets added to simulated gastric fluid with different nitrite concentrations, ranitidine conversion to NDMA was not detected until nitrite was 5000 μmol/L, which is 50-fold greater than the upper range of physiologic gastric nitrite concentrations at acidic pH. Researchers suggest ranitidine is not converted to NDMA in gastric fluid at physiologic conditions based on these findings.
According to an editorial, these two new FDA studies should serve to alleviate much of the previous concern about NDMA production of dimethylamine drugs in the human body. However, an in vitro study and a small phase 1 normal-participant study are far from definitive evidence. The in vitro stomach model still does not include numerous variables that can exist in a human stomach and may not reflect the scenario after a large acidic meal or one that includes chloramine-treated water. The phase 1 study provides more rigorous evidence, although additional studies will be needed to address several remaining unknown factors and better refine understanding of this area. It notes that even with the reassuring data from these, patients and clinicians should not expect the return of ranitidine to the market anytime soon, as ranitidine is not needed when other similarly effective H2 antagonists exist without the ability to form NDMA as they degrade in the medicine cabinet or enter the water supply.