title: Is local biotransformation the key to understanding the pharmacological activity of salicylates and gold drugs?
abstract: It is suggested that some drugs may be converted by inflammatory cells to yield active species. The transformation may be non-enzymatic, although being driven by the enzymatic production of highly reactive species which are normal products of activated leukocytes, such as singlet oxygen, hydrogen peroxide, hypochlorite, hydroxyl radical and nitric oxide. Drugs which may be transformed in this fashion are the anti-rheumatic gold complexes which may be converted either to aurocyanide or to Au(III) complexes by myeloperoxidase in polymorphonuclear leukocytes. Salicylate may also be activated by its oxidation to dihydroxybenzoates although evidence for its transformation is weaker than for the gold complexes.
authors.affiliation: School of Physiology and Pharmacology, University of New South Wales, Sydney, Australia.
authors.forename: M W
authors.initials: MW
authors.lastname: Whitehouse
authors.forename: G G
authors.initials: GG
authors.lastname: Graham
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001711:Biotransformation; D003485:Cyanates; D003486:Cyanides / Q000378:metabolism*; D006046:Gold; D017612:Gold Compounds / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006900:Hydroxylation; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology* / Q000378:metabolism; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000737:chemistry / Q000378:metabolism; D012459:Salicylates / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D003485:Cyanates; D003486:Cyanides; D017612:Gold Compounds; D012459:Salicylates; C043041:gold cyanide; D006046:Gold; D009195:Peroxidase