An intravenous loading dose of azathioprine decreases the time to response in patients with Crohn's disease.
OBJECTIVE
Azathioprine, an effective therapy for Crohn's disease, is limited by a prolonged time to response. The aim of this study was to determine the safety and utility of a loading dose of azathioprine to decrease the time to response in patients with Crohn's disease.


METHODS
Twelve patients were studied: 6 with 13 fistulae and 6 with inflammatory disease. All patients received an intravenous infusion of azathioprine (50 mg/h for 36 hours). Response was determined by physical and radiographic examination for fistulae and by the Crohn's Disease Activity Index for inflammatory disease. Erythrocyte concentrations of azathioprine metabolites were measured by chromatography.


RESULTS
Seven of 13 fistulae closed by week 4, and three had a temporary decrease in drainage. One fistula improved at week 16. Two fistulae failed to improve. Four of 6 patients with inflammatory disease achieved remission, and 1 improved temporarily. Improvement was rapid (< or = 4 weeks). Peak concentrations of azathioprine metabolites occurred within 3 days. Clinical response did not correlate with azathioprine metabolite concentrations at the azathioprine dose studied. No adverse events occurred.


CONCLUSIONS
An 1800-mg intravenous loading dose of azathioprine is safe and may decrease the time to response to < or = 4 weeks in patients with Crohn's disease. Correlation between clinical response and azathioprine metabolite concentrations at larger azathioprine doses should be determined.
D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006150:Guanine Nucleotides / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008297:Male; D008780:Methyltransferases / Q000097:blood; D008875:Middle Aged; D012074:Remission Induction; D013873:Thionucleotides / Q000097:blood; D013997:Time Factors
D006150:Guanine Nucleotides; D007166:Immunosuppressive Agents; D013873:Thionucleotides; C003964:6-thioguanylic acid; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine