Glutathione — pharmacology
Molecular targets, mechanism of action, pharmacokinetics and interactions as characterised in humans.
§2Pharmacology
§2.1Molecular targets
Table 2. Molecular targets recorded for Glutathione, with the character of the interaction and the potency where the Institute holds it.
| Target | Interaction | Note |
|---|---|---|
| Glutathione peroxidases and S-transferases | Substrate and cofactor | The principal intracellular thiol antioxidant and phase II conjugation cofactor |
| Reactive electrophiles | Direct conjugation | Non-enzymatic and enzymatic conjugation of electrophilic species |
§2.2Mechanism of action
Glutathione is the dominant intracellular low-molecular-weight thiol and the cofactor of the glutathione peroxidase and S-transferase systems. Administered glutathione is largely degraded extracellularly by gamma-glutamyl transpeptidase to its constituent amino acids, which are then taken up and used for intracellular resynthesis; the Institute notes that this makes cysteine availability, rather than glutathione administration, the rate-limiting consideration, and is the pharmacological rationale for N-acetylcysteine as an alternative.[1,2]
§2.3Pharmacokinetics
- Terminal half-life
- ≈10 min after intravenous administration
- Time to maximum concentration
- immediate on infusion
- Volume of distribution
- largely extracellular when administered
- Plasma protein binding
- not extensively bound
- Clearance
- rapid, largely renal and via gamma-glutamyl transpeptidase
- Bioavailability
- oral bioavailability of intact glutathione is low and contested
Extracellular hydrolysis by gamma-glutamyl transpeptidase and dipeptidases, with renal excretion. Intracellular concentrations are governed by de-novo synthesis, not by administered glutathione.
§2.4Interactions
- Cisplatin and other electrophilic chemotherapeutics — glutathione conjugation may reduce efficacy
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- D’Hondt M, Bracke N, Taevernier L, Gevaert B, Verbeke F, Wynendaele E, De Spiegeleer B. Related impurities in peptide medicines. Journal of Pharmaceutical and Biomedical Analysis 2014;101:2–30. doi:10.1016/j.jpba.2014.06.012 · PMID 25044089
- Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharmaceutical Research 2010;27(4):544–575. doi:10.1007/s11095-009-0045-6 · PMID 20143256
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.