title: Pharmacological properties of five diclofenac metabolites identified in human plasma.
abstract: Five metabolites of diclofenac sodium (Voltarol) have been identified in human plasma. All five metabolites were more than 50 times less potent than diclofenac in inhibiting PGE2 production in zymosan-stimulated mouse macrophages and LTC4 synthesis was not inhibited in these cells. Anti-inflammatory activity (adjuvant arthritis and carragheenan-induced paw oedema in rats) and analgesic activity (phenyl-p-benzoquinone writhing, mouse) of the metabolites were at least 10 times lower when compared to diclofenac. There was a good correlation between in vitro PGE2 inhibition and in vivo activities for diclofenac and its metabolites indicating that inhibition of prostaglandin synthesis is a major mechanism responsible for their pharmacological actions.
authors.affiliation: Research Department, Ciba-Geigy Ltd., Basel, Switzerland.
authors.forename: I
authors.initials: I
authors.lastname: Wiesenberg-Boettcher
authors.forename: J
authors.initials: J
authors.lastname: Pfeilschifter
authors.forename: A
authors.initials: A
authors.lastname: Schweizer
authors.forename: A
authors.initials: A
authors.lastname: Sallmann
authors.forename: P
authors.initials: P
authors.lastname: Wenk
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy; D004008:Diclofenac / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D004487:Edema / Q000188:drug therapy; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010146:Pain / Q000517:prevention & control; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000096:biosynthesis
chemical_list: D013189:SRS-A; D004008:Diclofenac; D015232:Dinoprostone