BACKGROUND: 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). AIM: To compare the pharmacokinetic (PK) profiles of PO and subcutaneous (SC) MTX in CD patients to determine the bioequivalence of these two routes. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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). AIM: To compare the pharmacokinetic (PK) profiles of PO and subcutaneous (SC) MTX in CDpatients to determine the bioequivalence of these two routes. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Christopher Andrew Lamb; Nicholas A Kennedy; Tim Raine; Philip Anthony Hendy; Philip J Smith; Jimmy K Limdi; Bu'Hussain Hayee; Miranda C E Lomer; Gareth C Parkes; Christian Selinger; Kevin J Barrett; R Justin Davies; Cathy Bennett; Stuart Gittens; Malcolm G Dunlop; Omar Faiz; Aileen Fraser; Vikki Garrick; Paul D Johnston; Miles Parkes; Jeremy Sanderson; Helen Terry; Daniel R Gaya; Tariq H Iqbal; Stuart A Taylor; Melissa Smith; Matthew Brookes; Richard Hansen; A Barney Hawthorne Journal: Gut Date: 2019-09-27 Impact factor: 23.059
Authors: Remo Panaccione; A Hillary Steinhart; Brian Bressler; Reena Khanna; John K Marshall; Laura Targownik; Waqqas Afif; Alain Bitton; Mark Borgaonkar; Usha Chauhan; Brendan Halloran; Jennifer Jones; Erin Kennedy; Grigorios I Leontiadis; Edward V Loftus; Jonathan Meddings; Paul Moayyedi; Sanjay Murthy; Sophie Plamondon; Greg Rosenfeld; David Schwartz; Cynthia H Seow; Chadwick Williams; Charles N Bernstein Journal: J Can Assoc Gastroenterol Date: 2018-07-10
Authors: Maryam Alkhatry; Ahmad Al-Rifai; Vito Annese; Filippos Georgopoulos; Ahmad N Jazzar; Ahmed M Khassouan; Zaher Koutoubi; Rahul Nathwani; Mazen S Taha; Jimmy K Limdi Journal: World J Gastroenterol Date: 2020-11-21 Impact factor: 5.742