Pharmacokinetic profiles for oral and subcutaneous methotrexate in patients with Crohn's disease

Wilson, Aze; Patel, Vishal; Chande, Nilesh; Ponich, Terry; Urquhart, Brad L.; Asher, Linda; Choi, Yun Hee; Tirona, Rommel G.; Kim, R. B.; Gregor, James C.

doi:10.1111/apt.12161

Cited by 30 publications

(15 citation statements)

References 13 publications

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“…For 6 of the patients enrolled in this study, information was available on the day the last dose of methotrexate was taken. No association was observed between time elapsed since the last dose of methotrexate and individual MTXGlu 2,3,4,5 or MTXGlu TOT levels. However, a rapid decline in MTXGlu 1 levels in RBCs after methotrexate administration was observed ( Figure 2).…”

Section: Resultsmentioning

confidence: 80%

“…No guidelines exist, however, on methotrexate standard dosing, route of administration, duration, and monitoring in IBD patients. There is also wide interpatient variability in concentrations of methotrexate and its active forms, which may be explained by age, renal function, absorption, dose, route of administration, and genetic polymorphisms in the folate pathway …”

mentioning

confidence: 99%

“…There is also wide interpatient variability in concentrations of methotrexate and its active forms, which may be explained by age, renal function, absorption, dose, route of administration, and genetic polymorphisms in the folate pathway. [4][5][6] Methotrexate is a folate antagonist that contains a single glutamate moiety. It is also known as MTX glutamate 1 (MTXGlu 1 ).…”

mentioning

confidence: 99%

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Methotrexate Polyglutamate Monitoring in Patients With Crohn's Disease

Fischer

Cook

Jones

et al. 2016

Clinical Pharm in Drug Dev

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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 (MTXGlu ) 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 MTXGlu levels were measured in red blood cells (RBCs) using high-performance liquid chromatography-mass spectrometry. No association was observed between RBC individual (MTXGlu ) 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 (MTXGlu ) concentrations compared with those with active disease, a definitive association between RBC MTXGlu levels and clinical disease activity could not be established. Larger longitudinal studies in patients with diverse disease activity are needed to establish the value of MTXGlu levels as indicators of treatment efficacy and clinical outcome.

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Section: Resultsmentioning

confidence: 80%

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confidence: 99%

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confidence: 99%

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Methotrexate Polyglutamate Monitoring in Patients With Crohn's Disease

Fischer

Cook

Jones

et al. 2016

Clinical Pharm in Drug Dev

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“…In CD, the bioavailability of oral methotrexate plateaus at approximately 15 mg/wk, and with subcutaneous administration, it increases linearly at higher dosages. 18,19 Our study had some limitations. First, central reading was not used to score the study endoscopies.…”

Section: Discussionmentioning

confidence: 93%

Methotrexate Is Not Superior to Placebo for Inducing Steroid-Free Remission, but Induces Steroid-Free Clinical Remission in a Larger Proportion of Patients With Ulcerative Colitis

et al. 2016

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“…Wilson et al [9] updated the Kurnik study using a more sensitive assay. They compared the pharmacokinetic profile of po and subcutaneous MTX (25 mg) in 11 CD patients.…”

Section: Mtx Pharmacokineticsmentioning

confidence: 99%

Use of methotrexate in inflammatory bowel disease in 2014: A User’s Guide

Swaminath¹

2014

WJGPT

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Methotrexate has been used an immunomodulator in many autoimmune diseases, including inflammatory bowel disease. However, many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bowel disease. We summarize the data for use of methotrexate in common clinical scenarios: (1) steroid dependant Crohn's disease (CD); (2) maintenance of remission in steroid free CD; (3) azathioprine failures in CD; (4) in combination therapy with Anti-TNF agents in CD; (5) decreasing antibody formation to Anti-TNF therapy in CD; (6) management of fistulizing disease in CD; and (7) as well as induction and maintenance of remission in ulcerative colitis. An easy to use algorithm is provided for the busy clinician to access and safely prescribe methotrexate for their inflammatory bowel disease patients.

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Pharmacokinetic profiles for oral and subcutaneous methotrexate in patients with Crohn's disease

Cited by 30 publications

References 13 publications

Methotrexate Polyglutamate Monitoring in Patients With Crohn's Disease

Methotrexate Polyglutamate Monitoring in Patients With Crohn's Disease

Methotrexate Is Not Superior to Placebo for Inducing Steroid-Free Remission, but Induces Steroid-Free Clinical Remission in a Larger Proportion of Patients With Ulcerative Colitis

Use of methotrexate in inflammatory bowel disease in 2014: A User’s Guide

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