Pharmacokinetics of intravenously administered glutathione in the rat

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Abstract
By means of an open two compartment model with a distribution and elimination phase, the pharmacokinetic properties of intravenously administered GSH (reduced glutathione) have been investigated in the rat. After a bolus injection of four various GSH doses (50 to 300 μmol kg−1), arterial plasma concentrations of GSH, GSSG (= oxidized glutathione), total thiols and soluble thiols minus GSH were elevated and then rapidly decreased non-exponentially. With increasing dose, the rate constant for drug elimination and plasma clearance increased from 0.84 to 2.44 ml min−1 and the half-life of the elimination phase decreased from 52.4 to 11.4 min. Both the apparent volume of distribution and the degree of penetration of GSH into the tissues were diminished with increasing dose (from 3.78 to 1.33 litres kg−1 and from 6.00 to 0.51 as k12/k21, respectively). The data indicate that GSH is rapidly eliminated. This is mainly due to rapid oxidation in plasma rather than by increased tissue extraction or volume distribution. Thus plasma GSH levels appear to be quickly regulated by which the body may maintain concentrations within narrow physiological limits.

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