Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties

Pharmacotherapeutic group: detoxifying agents for antineoplastic treatment, antidote for oxazaphosphorines
ATC Code: V03AF01

Mesna's uroprotectant mechanism of action is based on the stabilization of the urotoxic hydroxy metabolites of oxazaphosphorine and on the formation of non-toxic additive compounds with acrolein. These reactions enable regional detoxification in the kidneys and the efferent urinary tract.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

Mesna administered as a free thiol compound is rapidly converted in the serum to the mesna disulfide metabolite, a considerable proportion of which is reduced back to the free thiol compound following glomerular filtration. Excretion is almost exclusively via the kidneys. Renal elimination starts immediately after administration. In the first 4 hours after a single dose, excretion occurs primarily as a free SH compound, thereafter occurring almost exclusively in the form of disulfide. Renal elimination is largely completed within approximately 8 hours after administration.
The relevant compartment with regard to protection of the bladder is the urine, in which about 30 % of an intravenous dose is bioavailable in the form of free SH mesna.

In-vivo effect on lymphocyte counts
In pharmacokinetic studies in healthy volunteers, administration of single doses of mesna was commonly associated with a rapid (within 24 hours) and in some cases marked decrease in lymphocyte count, which was generally reversible within one week after administration. Data from studies with repeated dosing over several days are insufficient to characterize the time course of lymphocyte count changes.

In-vivo effect on serum phosphate levels
In pharmacokinetics studies in healthy volunteers, administration of mesna on single or multiple days was in some cases associated with moderate transient increases in serum phosphate concentration.
In addition, serum creatine phosphokinase (CPK) values were lower in samples taken 24 hours after mesna dosing than in pre-dosing samples. This might be due to significant interference with thiol (e.g., N-acetylcysteine) dependent enzymatic CPK tests.