title: Bioavailability of oral vs. subcutaneous low-dose methotrexate in patients with Crohn's disease.
abstract: BACKGROUND
  Oral methotrexate and folic acid are partly absorbed by a common intestinal transporter.
  
  
  OBJECTIVE
  : To determine the relative bioavailability of oral low-dose methotrexate administered with and without concomitant folic acid vs. subcutaneous administration in patients with stable Crohn's disease.
  
  
  METHODS
  Ten patients were randomized to receive their regular maintenance dose of methotrexate (15-25 mg) for three consecutive weeks: orally, orally with 5 mg folic acid or subcutaneously. Blood samples were drawn at specified intervals during 24 h, and methotrexate levels were determined by fluorescence immunoassay. Areas under the curve extrapolated to infinity (AUC infinity ) were compared between the three routes.
  
  
  RESULTS
  The geometric mean AUC infinity values (95% confidence intervals) were 360 nmol x h/L (301-430 nmol x h/L), 261 nmol x h/L (214-318 nmol x h/L) and 281 nmol x h/L (209-377 nmol x h/L) per milligram of methotrexate administered for subcutaneous, oral and oral with folic acid administration, respectively (P < 0.05 and P < 0.01 for oral with folic acid and oral vs. subcutaneous administration, respectively). The geometric mean relative bioavailabilities (95% confidence intervals) were 0.73 (0.62-0.86) and 0.77 (0.60-0.99) for oral and oral with folic acid administration, respectively (difference not significant).
  
  
  CONCLUSIONS
  In patients with stable Crohn's disease, the oral bioavailability of methotrexate is highly variable and averages 73% of that of subcutaneous administration. Concomitant folic acid has no significant effect on the bioavailability. Dose adjustments based on individual pharmacokinetic assessment should be considered when switching patients from parenteral to oral therapy.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Kurnik
authors.forename: R
authors.initials: R
authors.lastname: Loebstein
authors.forename: E
authors.initials: E
authors.lastname: Fishbein
authors.forename: S
authors.initials: S
authors.lastname: Almog
authors.forename: H
authors.initials: H
authors.lastname: Halkin
authors.forename: S
authors.initials: S
authors.lastname: Bar-Meir
authors.forename: Y
authors.initials: Y
authors.lastname: Chowers
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001682:Biological Availability; D003424:Crohn Disease / Q000378:metabolism*; D018592:Cross-Over Studies; D004338:Drug Combinations; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged
chemical_list: D004338:Drug Combinations; D005492:Folic Acid; D008727:Methotrexate