Pharmacological properties of five diclofenac metabolites identified in human plasma.
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.
Wiesenberg-Boettcher
I
I
Research Department, Ciba-Geigy Ltd., Basel, Switzerland.
Pfeilschifter
J
J
Schweizer
A
A
Sallmann
A
A
Wenk
P
P
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
D013189:SRS-A; D004008:Diclofenac; D015232:Dinoprostone