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

Abstract

Summary 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.