Pharmacokinetic profiles for oral and subcutaneous methotrexate in patients with Crohn's disease. Issue 3 (28th November 2012)

• Record Type: Journal Article
• Authors: Wilson, A.; Patel, V.; Chande, N.; Ponich, T.; Urquhart, B.; Asher, L.; Choi, Y.; Tirona, R.; Kim, R. B.; Gregor, J. C.
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 37:Issue 3(2013)
• Page Start: 340
• Page End: 345
• Publication Date: 2012-11-28
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.12161
• Languages: English
• ISSNs: 0269-2813

Abstract

<abstract abstract-type="main" xml:lang="en" id="apt12161-abs-0001"> <title>Summary</title> <sec id="apt12161-sec-0001" sec-type="section"> <title>Background</title> <p>Methotrexate (MTX) is administered subcutaneously to Crohn's Disease (CD) patients. There are very few studies evaluating the use of oral (PO) MTX in CD. A drug and its pharmaceutical alternative are equivalent (bioequivalence) when the bioavailability of the alternative falls within 80–125% of the bioavailability of the standard (US Food and Drug Administration ‐ FDA).</p> </sec> <sec id="apt12161-sec-0002" sec-type="section"> <title>Aim</title> <p>To compare the pharmacokinetic (PK) profiles of PO and subcutaneous (SC) MTX in CD patients to determine the bioequivalence of these two routes.</p> </sec> <sec id="apt12161-sec-0003" sec-type="section"> <title>Methods</title> <p>Eleven patients received a PO and an SC MTX dose (25 mg) separated by one week over a two‐week interval. Blood samples were collected at specified times over a 24‐h period for each patient on two separate days. MTX plasma levels were obtained using sensitive mass spectrometry. Areas under the curve (AUC) were compared between the two routes.</p> </sec> <sec id="apt12161-sec-0004" sec-type="section"> <title>Results</title> <p>The mean AUC values were 3375 ng/mL × h (PO MTX) and 3985 ng/mL × h (SC MTX). The mean AUC ratio (PO/SC) was 0.86 (0.62–1.08). This correlates with a relative PO bioavailability of 86% in comparison to SC. The 90% confidence interval for the mean AUC (PO/SC) ratio is (0.785, 0.929). There were no adverse events.</p> </sec> <sec id="apt12161-sec-0005" sec-type="section"> <title>Conclusions</title> <p>The mean MTX AUC (PO/SC) in these patients falls outside the 90% confidence interval for the bioequivalence limit. SC MTX is more bioavailable than PO MTX; however, the mean relative MTX bioavailability (PO/SC) nearly met the FDA bioequivalence standard and PO MTX could be proposed in responders who would prefer this route.</p> </sec> </abstract>