A higher dose requirement of tacrolimus in active Crohn's disease may be related to a high intestinal P-glycoprotein content.
Tacrolimus, a relatively new therapeutic option for patients with corticosteroid-refractory Crohn's disease or ulcerative colitis, is a substrate for the apically directed efflux transporter P-glycoprotein (P-gp). Duodenal biopsy specimens obtained from a patient with corticosteroid-refractory Crohn's disease and with significantly higher-than-average tacrolimus dose requirements were analyzed for P-gp by Western blot. The P-gp content in this patient was more than double that in specimens obtained from 9 of 10 healthy subjects. Elevated intestinal P-gp could have resulted in decreased tacrolimus absorption, thereby leading to decreased blood concentration and decreased efficacy in this patient. The cause and prevalence of this phenomenon are unknown.
Buchman
Alan L
AL
Division of Gastroenterology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA. a-buchman@northwestern.edu
Paine
Mary F
MF
Wallin
Anita
A
Ludington
Shana S
SS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D015746:Abdominal Pain / Q000175:diagnosis / Q000209:etiology; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D015153:Blotting, Western; D003424:Crohn Disease / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000175:diagnosis / Q000209:etiology; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007413:Intestinal Mucosa / Q000473:pathology; D011379:Prognosis; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016559:Tacrolimus / Q000008:administration & dosage*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015415:Biomarkers; D007166:Immunosuppressive Agents; D016559:Tacrolimus