Comment by rao-v
12 hours ago
Could somebody package Tylenol with a sufficient amount of NAC to de-risk it? I suspect such a formulation would not require trials?
12 hours ago
Could somebody package Tylenol with a sufficient amount of NAC to de-risk it? I suspect such a formulation would not require trials?
Certain esters have been found to be much safer (in mice, at least):
> The glutathione hepatic values in mice obtained by intraperitoneal injection of the ester are superimposable on controls and the oral LD50 was found to be greater than 2000 mg kg^-1 and the intraperitoneal LD50 was 1900 mg kg^-1 ...
That's for pyroglutamic and glutamic acid esters of paracetamol: https://pubmed.ncbi.nlm.nih.gov/8799871/
and more general analogs apparently can also be designed to not produce NAPQI:
> Thus, in 2020, N-sulpharyl-APAP prodrugs 39–40 (Fig. 11) were developed. [...] They are not hepatotoxic because they do not generate toxic metabolite NAPQI, even in concentrations equal to a toxic dose of APAP (600 mg kg^−1 in mice).
https://pubs.rsc.org/zh-tw/content/articlepdf/2024/ra/d4ra00... p. 9702.
These would probably require trials, though.
See superscript 6 on the article. Apparently NAC might has side effects of its own.
One of the side effects in a study in mice was inducing lung cancer: https://doi.org/10.1172/jci.insight.127647