PHARMACOKINETICS OF INTRAVENOUS AND ORAL SODIUM 2-MERCAPTOETHANE SULFONATE (MESNA) IN NORMAL SUBJECTS
PHARMACOKINETICS OF INTRAVENOUS AND ORAL SODIUM 2-MERCAPTOETHANE SULFONATE (MESNA) IN NORMAL SUBJECTS
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DOI：
10.1111/j.1365-2125.1987.tb03092.x
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发表时间：
1987-05-01
影响因子：
3.4
通讯作者：
ROGERS, HJ
中科院分区：
文献类型：
--
作者：
JAMES, CA;MANT, TGK;ROGERS, HJ
1 The pharmacokinetics of mesna (sodium 2-mercaptoethane sulphonate) and its inactive disulphide, dimesna, were investigaged using high performance liquid chromatography in six normal subjects following intravenous and oral administration of 800 mg mesna. 2 The mean maximum mesna concentration after i.v. administration was 111 (s.d. .+-. 28.3) nmol-1 and the mean maximum dimensa concentration was 183 (s.d. .+-. 41.6) nmol ml-1. Following oral mesna dosing the mean peak mesna concentraion 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. 3 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) 1 kg-1. The mean half-life of dimensa was 1.17 (s.d. .+-. 0.32) h. It was not possible to determine their half-lives after oral mesna administration. 4 The mean mesna concentraion in the 0.sbd.4 urine collection was 9.6 (s.d. .+-. 10.7; range 1.4.sbd.23.7) nmol ml-1 following i.v. mesna injection. After oral mesna the highest mesna concentration occurred in either the 0.sbd.4 or 4.sbd.8 h urine collections. The mean peak mesna concentration was 2.5 (s.d. .+-. 1.7) .mu.mol ml-1 (c.f. estimated uroprotective concentration of 1.7 .mu.mol ml-). 5 The mean 4 h urinary clearance of the uroprotective species mesna was 0.413 (s.d. .+-. 0.136) 1 kg-1 h-1. After both i.v. and oral mesna the urinary excretion of mesna is predominantly during the first 4 h. The urinary availability as mesna alone after oral dosing was 53.0 .+-. 19.5% of that following i.v. administrtion. 6 It should be possible to use oral mesna as a uroprotective agent in conjunction with oxazaphosphorine treatment either by giving an oral dose of 40% of the cytotoxic dose 2 h before the cytotoxic or using both i.v. (20% cytotoxic dose) and oral (40% cytotoxic dose) mesna doses with the exaxaphosphorine followed by oral mesna (40% of oxazaphosphorine dose) every 4 h.
