Comparative efficacy and toxicity of 10-ethyl-10-deazaaminopterin and methotrexate in a mycobacterial rat arthritis model.
OBJECTIVE
To compare the efficacy and toxicity of the newer antifolate 10-ethyl-10-deazaaminopterin (10-EDAM) with methotrexate (MTX) in an animal model of inflammatory arthritis.


METHODS
Groups of 8 or 9 female Lewis rats received intraperitoneal (ip) Mycobacterium butyricum to induce arthritis, and then one of the antifolates at either 1.0 mg/kg/day by oral gavage or 0.2 mg/kg/2 days ip until 25 days post-induction. Treatment groups were compared with control arthritic and non-arthritic animals. Efficacy was assessed by changes in weight, paw volume, and paw diameter, as well as maximum arthritis index, plasma albumin and plasma iron levels. Toxicity was documented for all groups.


RESULTS
10-EDAM was as effective as MTX at identical doses in preventing arthritis. 10-EDAM produced less toxicity than MTX at the higher dose used but similar toxicity at the lower dose.


CONCLUSIONS
10-EDAM may provide an alternative antifolate therapy in the clinical management of inflammatory arthritis, and appears to be less toxic than MTX.
Skeith
K J
KJ
Division of Rheumatology, University of Alberta, Edmonton, Canada.
Ramos-Remus
C
C
Russell
A S
AS
D000630:Aminopterin / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D005260:Female; D007410:Intestinal Diseases / Q000139:chemically induced; D008727:Methotrexate / Q000627:therapeutic use* / Q000633:toxicity; D009170:Nontuberculous Mycobacteria; D010538:Peritonitis / Q000139:chemically induced; D051381:Rats; D011917:Rats, Inbred Lew; D013280:Stomatitis / Q000139:chemically induced
C040210:edatrexate; D000630:Aminopterin; D008727:Methotrexate