Excretion of sodium 2-mercaptoethanesulphonate (MESNA) in the urine of volunteers after oral dosing

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

doi:10.1016/0277-5379(85)90079-3

Cited by 16 publications

(5 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result suggests that very little mesna, if any, is excreted in the urine as a mesna adduct with other sulphydryl compounds such as cysteine. Jones et al (1985) found a mean of 24.2 (s.d. 9.0)% of an oral dose of 400 mg mesna to be excreted as free sulphydryl groups by three subjects (two subjects studied twice).…”

Section: Resultsmentioning

confidence: 99%

“…The pharmacokinetics of mesna and dimesna have never been satisfactorily studied in man. This is largely because a suitable analytical method for these compounds has not been available and previous studies (Burkert et al, 1984;Jones et al, 1985) have had to rely upon the relatively imprecise colorimetric Ellman free thiol assay (Ellman, 1959). We have recently developed a high performance liquid chromatographic assay (James & Rogers, 1986) which has allowed a pharmacokinetic investigation of this important adjuvant to cytotoxic chemotherapy to be carried out and we present the results of these studies below.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics of intravenous and oral sodium 2‐mercaptoethane sulphonate (mesna) in normal subjects.

James

Mant

Rogers

1987

Brit J Clinical Pharma

View full text Add to dashboard Cite

The pharmacokinetics of mesna (sodium 2‐mercaptoethane sulphonate) and its inactive disulphide, dimesna, were investigated using high performance liquid chromatography in six normal subjects following intravenous and oral administration of 800 mg mesna. The mean maximum mesna concentration after i.v. administration was 111 (s.d. +/‐ 28.3) nmol ml‐1 and the mean maximum dimesna concentration was 183 (s.d. +/‐ 41.6) nmol ml‐1. Following oral mesna dosing the mean peak mesna concentration was 19.6 (s.d. +/‐ 10.2) nmol ml‐1 but mesna was only found in the plasma of five of the six subjects. The mean peak dimesna concentration was 22.5 (s.d. +/‐ 12.4) nmol ml‐1. Following i.v. mesna administration, the mean half‐life of mesna was 21.8 (s.d. +/‐ 3.1) min and total body clearance 1.23 (s.d. +/‐ 0.31) l kg‐1 h‐1. The mean half‐ life of dimesna was 1.17 (s.d. +/‐ 0.32) h. It was not possible to determine their half‐lives after oral mesna administration. The mean mesna concentration in the 0‐4 h urine collection was 9.6 (s.d. +/‐ 10.7; range 1.4‐28.7) nmol ml‐1 following i.v. mesna injection. After oral mesna the highest mesna concentration occurred in either the 0‐4 or 4‐8 h urine collections. The mean peak mesna concentration was 2.5 (s.d. +/‐ 1.7) mumol ml‐1 (c.f. estimated uroprotective concentration of 1.7 mumol ml‐1). The mean 4 h urinary clearance of the uroprotective species mesna was 0.413 (s.d. +/‐ 0.136) l kg‐1 h‐1. After both i.v. and oral mesna the urinary excretion of mesna is predominantly during the first 4 h.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of intravenous and oral sodium 2‐mercaptoethane sulphonate (mesna) in normal subjects.

James

Mant

Rogers

1987

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…In addition, mesna resulted in a marked increase in the urinary excretion of cyst(e)ine. Mesna is in part excreted in the form of mesna-cysteine disulfide and may also circulate as a mixed disulfide (Jones et al, 1985;Duran et al, 1981). This fraction appears to be larger after oral administration such that more cyst(e)ine is lost via the kidneys following oral administration.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

mentioning

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

“…(Sidau & Shaw, 1984;Jones et al, 1985). Phosphoramide mustard was isolated from the ['4C]CP kidney-slice incubation medium and identified by mass spectrometry.…”

mentioning

confidence: 99%