Mesna Stada Mechanism of Action

Substance or indication group: Sodium 2-mercaptoethanesulphonate. Antidote to oxazaphosphorines.
Pharmacology: Pharmacodynamics: The mode of action of the uroprotector mesna is based on the stabilisation of the urotoxic hydroxy metabolites of oxazaphosphorines on the one hand and on the other hand on formation of non-toxic compounds with acrolein. A regional detoxification in the kidneys and the lower urinary tract is achieved due to this reaction.
Pharmacokinetics: Following administration, the mesna monomer (free thiol compound) is rapidly metabolised to mesna disulphide (dimesna) in serum, which is again reduced in considerable amounts to the free thiol compound following glomerular filtration.
Mesna is almost exclusively eliminated via the kidneys and hardly via the bile. Following administration, renal elimination begins immediately and is largely completed after 8 hours. Within the first 4 hours after administration, mesna is mainly eliminated as free SH compound and then almost exclusively in form of the disulphide (dimesna).
Bioavailability: With regard to protection of the urinary bladder, the relevant compartment is the urine, where approx. 30% is bioavailable as free SH mesna after intravenous administration.
Toxicology: Preclinical safety data: Mesna is a pharmacologically and physiologically almost inert and non-toxic thiol compound which is excreted rapidly via the kidneys and does not penetrate tissues. In animal experiments, mesna showed no mutagenic, carcinogenic or teratogenic properties.
Acute toxicity: The LD₅₀ in male and female mice as well as in male and female rats is on average 1929 mg/kg i.v.; 1720 mg/kg i.p., 5605 mg/kg p.o.
Chronic toxicity: In preclinical studies in several animal species (rat, rabbit and dog) mesna showed very low chronic toxicity.