Excretion of disodium Bis-2-mercaptoethanesulphonate (dimesna) in the urine of volunteers after oral dosing

Shaw, Ian C.; Weeks, M.S.

doi:10.1016/0277-5379(87)90338-5

Cited by 11 publications

(7 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This LLQ value is lower than previously reported ranges for mesna and BNP7787 using other analytical detection methods [24,[26][27][28]30]. In addition, the lower limit of detection (LLD) for both mesna and BNP7787 was approximately 250 nM in plasma with manually determined signal to noise ratios of approximately 2:1 for BNP7787 and approximately 3:1 for mesna.…”

Section: Llq Linearity and Lldcontrasting

confidence: 61%

“…Ellman's reagent can be used to convert thiols to the mixed disulfides that can be separated and detected by HPLC [18]; however, like other approaches utilizing chemical derivatization, this approach has low sensitivity and is limited by interference due to endogenous thiols in plasma. A fluorescence-based method in which thiols are converted to monobromobimane derivatives prior to the chromatography step has also been developed [19], and while this was a notable advance, an important limitation of this method was that photodegradation products of monobromobimane were also fluo- [30,36,40]. Once BNP7787 is administered, a thiol, RSH where R = glutathione, cysteine, homocysteine, cysteinyl-glutamate or cysteinyl-glycine may attack BNP7787 resulting in the heterolytic cleavage of BNP7787's disulfide bond, producing free mesna and a mesna-thiol mixed disulfide, M-S-S-R where R is glutathione, cysteine, homocysteine, cysteinyl-glutamate or cysteinyl-glycine.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Analysis of BNP7787 thiol-disulfide exchange reactions in phosphate buffer and human plasma using microscale electrochemical high performance liquid chromatography

Shanmugarajah

Ding

Huang

et al. 2009

Journal of Chromatography B

View full text Add to dashboard Cite

Section: Llq Linearity and Lldcontrasting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Analysis of BNP7787 thiol-disulfide exchange reactions in phosphate buffer and human plasma using microscale electrochemical high performance liquid chromatography

Shanmugarajah

Ding

Huang

et al. 2009

Journal of Chromatography B

View full text Add to dashboard Cite

“…Since oral mesna increases circulating free cysteine to a lesser extent than intravenous mesna and leads to a more marked increase in urinary cyst(e)ine which may contribute to uroprotection, oral administration of mesna may be preferable. In view of the fact that the efficacy of mesna critically depends on the reduction by the kidneys of mesna-mixed disulfides and dimesna a case could be made for the therapeutic use of dimesna which exhibits comparable uroprotective properties as mesna (Shaw & Weeks, 1987) but is not likely to interfere with thiol homeostasis to the same extent as mesna. …”

Section: Discussionmentioning

confidence: 99%

Depletion of circulating cyst(e)ine by oral and intravenous mesna

Stofer-Vogel

Cerny²,

Küpfer³

et al. 1993

Br J Cancer

View full text Add to dashboard Cite

Summary The sulfhydryl status of normal and tumour cells is critically important in determining their susceptibility to various cytostatic agents. As a sulfhydryl compound, mesna (sodium 2-mercaptoethanesulfonate) which is used in large doses to prevent haemorrhagic cystitis associated with certain chemotherapeutic regimens might derange cellular thiol homeostasis. In order to investigate the effects of mesna on the concentrations of thiols in plasma, cysteine, glutathione and their disulfides were measured by HPLC following the oral and intravenous administration of mesna to healthy volunteers. After 7.3 mmol mesna i.v. free cysteine rose from 8.2 (95% CI 7.0-9.4) nmol ml' to 53.6 (47.4-59.8) nmol ml-' at 5 min, most likely due to reduction of circulating cystine by the sulfhydryl drug. This initial rise was followed by a marked decrease of total cyst(e)ine in plasma from 276 (215-337) nmol ml-' to a nadir of 102 (McGown & Fox, 1986). Similarly, the sulfhydryl status of normal cells is an important determinant of their defense against the toxic effects of the same cytostatic drugs (Chasseaud, 1979). Mesna (sodium 2-mercaptoethanesulfonate) is increasingly used to prevent haemorrhagic cystitis associated with chemotherapeutic regimens containing high doses of ifosfamide and cyclophosphamide (Dechant et al., 1991). Although mesna is very polar and does not passively enter cells to a significant extent (Ormstad et al., 1983), the sulfhydryl drug could still markedly affect cellular thiol homeostasis. High concentrations of the sulfhydryl could reduce circulating cystine, thereby making more cysteine available to cells since cysteine is more readily taken up by many cell types than cystine (Issels et al., 1988). In addition, cysteine-mesna mixed disulfides have been identified in urine (Jones et al., 1985;Duran et al., 1981). Mesna might thus result in a substantial loss of cyst(e)ine. Since the effects of intravenous and oral mesna on circulating physiological thiols are not known and the mesna-induced loss of cyst(e)ine has not been quantitated, the concentrations of cysteine, glutathione and their disulfides in plasma and urine were measured following the oral and intravenous administration of mesna to healthy volunteers. Subjects and methodsThe effects of mesna (sodium-2-mercaptoethane-sulfonate) on plasma cyst(e)ine and glutathione after intravenous and oral administration were studied in eight healthy volunteers, two females and six men, 24 to 39 years of age, all within 10% of ideal body weight. Informed consent was obtained from each of the participants. The study was approved by the ethics committee of the local medical school. After an overnight fast an indwelling catheter was placed into an antecubital vein of both arms in order to obtain blood repeatedly without tourniquet. Two blood samples were obtained 10 min apart before the administration of mesna in order to determine the basal concentrations of glutathione and cyst(e)ine.Intravenous mesna was infused over 2 min at a dose of 1.2 g (7.3 mmol; AS...

show abstract

“…The reduced thiol concentration was determined by the spectrophotometric method based on the use of Ellman's reagent [15][16][17] using the extinction coefficient at 412 nm for 2-nitro-5-thiobenzoic acid with correction for absorbance of a reagent blank. The concentration of reduced thiols found after the treatment by either mesna or amifostine (i.e.…”

Section: Metabolite Assaysmentioning

confidence: 99%

In vivo mesna and amifostine do not prevent chloroacetaldehyde nephrotoxicity in vitro

et al. 2008

View full text Add to dashboard Cite

Chloroacetaldehyde (CAA) is the putative metabolite responsible for ifosfamide-induced nephrotoxicity. Whereas evidence suggests that sodium 2-mercaptoethanesulfonate (mesna) and amifostine protect renal cells against CAA toxicity in vitro, their efficacy in clinical studies is controversial. To better understand the discrepancy between in vivo and in vitro results, we combined the in vivo intraperitoneal administration of either saline or mesna (100 mg/kg) or amifostine (200 mg/kg) in rats and the in vitro study of CAA toxicity to both proximal tubules and precision-cut renal cortical slices. The measured renal cortical concentrations of mesna and amifostine were 0.6+/-0.1 micromol/g and 1.2+/-0.2 micromol/g, respectively; these drugs did not cause renal toxicity. Despite this, none of the adverse effects of 0.5 mM CAA was prevented by the previous in vivo administration of mesna or amifostine. Toxicity of 0.5 mM CAA to rat proximal tubules was shown by the fall of cellular adenosine triphosphate (ATP), total glutathione and coenzyme A + acetyl-coenzyme A levels and by the altered metabolic viability of renal cells. Long-term exposure of cortical slices to CAA concentrations > or =30 microM caused severe cell toxicity (i.e. decrease in cellular ATP, total glutathione, and coenzyme A + acetyl-coenzyme A levels), which was not prevented by the in vivo administration of mesna or amifostine.

show abstract

Excretion of disodium Bis-2-mercaptoethanesulphonate (dimesna) in the urine of volunteers after oral dosing

Cited by 11 publications

References 4 publications

Analysis of BNP7787 thiol-disulfide exchange reactions in phosphate buffer and human plasma using microscale electrochemical high performance liquid chromatography

Analysis of BNP7787 thiol-disulfide exchange reactions in phosphate buffer and human plasma using microscale electrochemical high performance liquid chromatography

Depletion of circulating cyst(e)ine by oral and intravenous mesna

In vivo mesna and amifostine do not prevent chloroacetaldehyde nephrotoxicity in vitro

Contact Info

Product

Resources

About