Hepatic methotrexate content and progression of hepatic fibrosis: preliminary findings.
Liver tissue from 16 patients with rheumatoid arthritis was studied. The patients had received low dose methotrexate weekly for a minimum of 12 months between two liver biopsies. The progression of pericellular fibrosis was measured by computerised image analysis. Extracts of these liver biopsy specimens were pooled into five samples according to the progression of hepatic fibrosis and analysed by high performance liquid chromatography. The concentrations of methotrexate, 2,4 diamino-N(10)-methylpteroic acid, and methotrexate polyglutamate were markedly increased in the samples obtained from the three patients who recorded the greatest increase in fibrosis. These preliminary data suggest that progression of hepatic fibrosis is related to the retention of methotrexate and metabolites in the liver.
Ahern
M J
MJ
Department of Medicine, Flinders University of South Australia.
Kevat
S
S
Hill
W
W
Hayball
P J
PJ
Harley
H
H
Hall
P D
PD
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005355:Fibrosis; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008099:Liver / Q000737:chemistry* / Q000187:drug effects / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000031:analogs & derivatives / Q000032:analysis* / Q000627:therapeutic use; D008875:Middle Aged; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000032:analysis
C000203:deoxyaminopteroic acid; D011099:Polyglutamic Acid; C014085:methotrexate polyglutamate; D008727:Methotrexate