title: Pharmacokinetic profiles for oral and subcutaneous methotrexate in patients with Crohn's disease.
abstract: 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).
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of Western Ontario, 800 Commissioners Road E., London, ON, Canada. awilson2008@meds.uwo.ca
authors.forename: A
authors.initials: A
authors.lastname: Wilson
authors.forename: V
authors.initials: V
authors.lastname: Patel
authors.forename: N
authors.initials: N
authors.lastname: Chande
authors.forename: T
authors.initials: T
authors.lastname: Ponich
authors.forename: B
authors.initials: B
authors.lastname: Urquhart
authors.forename: L
authors.initials: L
authors.lastname: Asher
authors.forename: Y
authors.initials: Y
authors.lastname: Choi
authors.forename: R
authors.initials: R
authors.lastname: Tirona
authors.forename: R B
authors.initials: RB
authors.lastname: Kim
authors.forename: J C
authors.initials: JC
authors.lastname: Gregor
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D003424:Crohn Disease / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D009864:Ontario; D013810:Therapeutic Equivalency
chemical_list: D007166:Immunosuppressive Agents; D008727:Methotrexate