Methotrexate Polyglutamate Monitoring in Patients With Crohn's Disease.
Methotrexate is an efficacious immunosuppressant for induction and maintenance of remission in Crohn's disease. The goal of this pilot study was to determine whether total or individual methotrexate glutamate levels (MTXGlun) in red blood cells correlate with disease activity and adverse events in Crohn's disease. A cross-sectional study was undertaken with 12 patients on a stable dose of 25 mg weekly methotrexate (oral or subcutaneous). Clinical disease activity was assessed by the Harvey-Bradshaw Index (HBI), and biologic disease activity was measured by inflammatory markers. Concentrations of individual MTXGlunlevels were measured in red blood cells (RBCs) using high-performance liquid chromatography-mass spectrometry. No association was observed between RBC individual (MTXGlun) or total methotrexate glutamate concentrations and clinical disease activity (HBI score) or inflammatory markers or adverse events. Although Crohn's disease patients in remission appeared to generally have higher RBC total longer-chain methotrexate polyglutamate (MTXGlu3+4+5) concentrations compared with those with active disease, a definitive association between RBC MTXGlu3+4+5levels and clinical disease activity could not be established. Larger longitudinal studies in patients with diverse disease activity are needed to establish the value of MTXGlunlevels as indicators of treatment efficacy and clinical outcome.
Indiana University Division of Gastroenterology and Hepatology, Indianapolis, IN, USA.
Monika
M
Fischer
Indiana University Division of Gastroenterology and Hepatology, Indianapolis, IN, USA.
Shivi
S
Siva
Indiana University Division of Gastroenterology and Hepatology, Indianapolis, IN, USA.
Gwendolyn K
GK
Cook
Indiana University Department of Medicine, Indianapolis, IN, USA.
David R
DR
Jones
College of Pharmacy and Health Sciences, Butler University, Indianapolis, IN, USA.
Hala M
HM
Fadda
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D003424:Crohn Disease / Q000188:drug therapy*; D003430:Cross-Sectional Studies; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D008875:Middle Aged; D010865:Pilot Projects; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000097:blood; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome
D011099:Polyglutamic Acid; C014085:methotrexate polyglutamate; D008727:Methotrexate
bioavailability; immunosuppressant; inflammatory bowel disease; methotrexate polyglutamate; therapeutic drug monitoring