[ENGINA]

This drug is taken as an anti-inflammatory to manage some bowel diseases. The maximum dosage is around 4000mg/day, but if someone were to overdose with 8000mg/day for a week, which organ(s) would be affected by this? Would the skin be affected in any way? Also, would the damage be reversible?

I would try to answer this question myself, but I don't know anything about this compound's method of action, or how it interacts with the body. Any help would be appreciated.

[Babcock_Hall]

This compound is also known as mesalamine, among other names.  Apparently, its mechanism of action is not known, but it may work by inhibiting the synthesis of prostaglandins.  I am not a medical doctor, but if you want an offhand opinion, it looks to me as if the kidneys or liver might be the most likely organs to be affected.

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000880/
http://www.medicinenet.com/mesalamine/article.htm
http://colitis.emedtv.com/mesalamine/mesalamine-warnings-and-precautions.html

[ENGINA]

I see. It turns out that mesalamine is metabolized into N-acetyl-5-aminosalicylic acid (Ac-5-ASA). What's the difference, if any?

Also, is Ac-5-ASA harmful or carcinogenic? i.e., can it alter or damage the DNA of any cells it comes into contact with?

[fledarmus]

This might answer some of your questions:

http://www.aptalispharma.com/pdf/salofalk.pdf

According to that monograph, the kidneys might be expected to show the first signs of damage, but not until you reached 8 to 10 times the normal dose. As of 2004, the authors are saying that no actual cases of kidney damage caused by the drug have been reported. They show no indication of cancer in rat tests out to 2-1/3 years. The metabolite and the parent compound have similar half-lives in serum, so toxicity testing for the parent compound would also have shown any toxicity effects of the metabolite.

There is some suggestion that 5-ASA taken with aspirin may be worse than either of the two taken separately.

[ENGINA]

Would the rats have produced the same metabolites? I don't know how biologically similar they are to us.