Disposition of glutathione monoethyl ester in the rat: glutathione ester is a slow release form of extracellular glutathione

Glutathione monethyl ester (GSHE) is thought to deliver gluta-thione (GSH) directly and intact into cell cytosol and therefore might have therapeutic potential in states of GSH deficiency. To better understand the disposition of GSHE, the pharmacokinet-ics of GSHE and GSH were compared in rats. Fifteen mm after an i.v. dose of 5 mmol/kg GSHE, the plasma concentration of GSHE was 7.2 ± 1.2 mmol/l and the plasma concentration of GSH had increased from 0.009 ± 0.002 to 2.5 ± 0.3 mmot/1. The areas under the plasma concentration time curves of GSH were identical after either the administration of GSHE or GSH, but the mean residence time of GSH in plasma was significantly longer after GSHE. The concentration of GSHE in liver reached a peak of 0.66 ± 0.09 moVg. Intrahepatic concentrations of cysteine and GSH increased from 53 ± 1 5 to 31 9 ± 41 nmol/