Concentrations Of Mesna Research Articles

Depletion of total cysteine, glutathione, and homocysteine in plasma by ifosfamide/mesna therapy.

The sulfhydryl status of cells, particularly the intracellular concentration of glutathione, is a critical determinant of the response of tumor and normal cells to cytostatic drugs. Recent data indicate that the administration of mercaptoethane sulfonate (mesna), which is often combined with ifosfamide, markedly decreases the circulating concentration of total cysteine and could thereby influence the response of the organism to the cytotoxic effects of chemotherapy. The aim of the present study was to assess the effects of the combination of ifosfamide/mesna on sulfhydryl and disulfide homeostasis in tumor patients. Ifosfamide was infused into 14 patients with advanced sarcoma for 5 days at a dose of 2.4-3.2 g/m2 per day together with mesna. The plasma concentrations of total mesna, cysteine, glutathione, and homocysteine were measured before and on days 1 and 6 of the first course of ifosfamide/mesna therapy and prior to the next course of chemotherapy, and the urinary excretion of cysteine and mesna was monitored daily using a high-performance liquid chromatography (HPLC) method. Ifosfamide/mesna resulted in a marked depletion of circulating total cysteine, i.e., cysteine, cystine, and cysteine mixed disulfides [from 245 +/- 36 to 50 +/- 14 nmol/ml (mean +/- 95% CI) on day 6], total glutathione (from 6.9 +/- 1.1 to 2.5 +/- 1.1 nmol/ml), and total homocysteine (from 12.3 +/- 2.1 to 1.4 +/- 1.1 nmol/ml). The values returned to baseline levels prior to the next course of chemotherapy. The urinary excretion of cysteine increased significantly from 0.28 to 1.82 mmol/day on the 1st day, whereupon it returned toward baseline. An average of 62% +/- 6% of the delivered dose of mesna was recovered in urine. The combination of ifosfamide/mesna results in depletion of circulating total cysteine, glutathione, and homocysteine. This marked derangement of sulfhydryl and disulfide homeostasis could modulate the efficacy and toxicity of ifosfamide/mesna therapy.

Oral bioavailability of mesna tablets.

To test the feasibility of uroprotection with sodium 2-mercaptoethane-sulfonate (mesna) in tablet form the bioavailability of mesna tablets was determined in healthy volunteers by HPLC. The area under the plasma concentration-time curve (AUC) of free mesna was significantly lower following oral (110 mumol.l-1 x h-1; 95% CI 98-122) than following i.v. administration of 1.2 g of mesna (201 mumol.l-1 x h-1; 95% CI 158-244). The AUC for total mesna, i.e. dimesna and mixed disulfides, however, were comparable in the two groups, with 628 (539-717) and 772 (713-831) mumol.l-1 x h-1, respectively. The mean residence time was significantly longer following oral mesna, at 79 (76-83) min vs 239 (229-250) min. Following oral mesna 51.1% (46.2-56.0%) of the administered dose was recovered in the urine in 24 h, compared with 60.6 (53.6-67.6)% in 4 h following i.v. mesna, and the average concentration of mesna in the urine exceeded 3 mmol.l-1 for 8 h. The data indicate that mesna in tablet form has an adequate bioavailability for uroprotection and therefore may be preferable to liquid mesna, which has an unpleasant taste. Oral mesna has a longer mean residence time than i.v. mesna, which means that uroprotection can be achieved with longer dosing intervals.

The stability of mesna in beverages and syrup for oral administration

We evaluated the stability of the aqueous formulation of mesna during storage in syringes and after dilution in beverages and syrups. Measurements of the concentrations of mesna showed that the undiluted formulation was stable for at least 9 days in standard polypropylene syringes at 5 degrees, 24 degrees, and 35 degrees C. There was no detectable oxidation of mesna to dimesna over the course of at least 1 week when mesna was diluted 1:2 and 1:5 in syrups and incubated at 24 degrees C in capped tubes. Concentration changes were clinically negligible for 1:2, 1:10, and 1:100 dilutions of mesna in six carbonated drinks, two juices, and milk after incubation for 24 h at 5 degrees C. Thus, the aqueous mesna formulation is stable when diluted and stored in a variety of beverages and syrups under conditions suitable for oral administration.