Effect of chronic administration of tacrolimus and cyclosporine on human gastrointestinal permeability.
The antirejection drug tacrolimus (FK506) has been reported to impair intestinal permeability in an early stage after orthotopic liver transplantation (OLT), and cyclosporine (CsA) has shown a similar effect in animals. We studied the chronic effect of FK506 and CsA on gastroduodenal and intestinal permeability and on blood endotoxin levels in patients 2 to 3 years after OLT. Thirty-two OLT patients (22 men and 10 women; mean age, 44.8 +/- 7.1) who had received CsA (n = 19) or FK506 (n = 13) and 10 healthy volunteers (6 male and 4 female, mean age 41.7 +/- 5.4) were assessed for gastroduodenal permeability by recovery in urine of sucrose after oral administration and for intestinal permeability by recovery in urine after oral loads of rhamnose and lactulose, which evaluate the intracellular and paracellular routes, respectively. In all subjects, plasma levels of endotoxins also were assessed. Gastroduodenal permeability was similar in patients and controls (0.03 +/- 0.003 versus 0.04 +/- 0.01%, P = NS). In regard to intestinal permeability, passage through the intracellular route was significantly reduced in OLT patients compared with controls (1.13 +/- 0.06 versus 2.74 +/- 0.17%, P <.01), but paracellular permeability was unchanged (0.14 +/- 0.007 versus 0.13 +/- 0.01%, P = NS). Serum endotoxin levels were similar in all subjects. We conclude that chronic administration of FK506 or CsA induces a clinically irrelevant, selective dysfunction of monosaccharide absorption, but does not affect gastroduodenal or intestinal permeability.
Department of Clinical and Experimental Medicine, Division of Hepatogastroenterology, University of Naples Federico II, Naples, Italy. giparril@tin.it
Gianpaolo
G
Parrilli
Cristiana
C
Abazia
Giovanni
G
Sarnelli
Maria Michela
MM
Corsaro
Pietro
P
Coccoli
Lucia
L
Viglione
Rosario
R
Cuomo
Gabriele
G
Budillon
D000293:Adolescent; D000328:Adult; D016572:Cyclosporine / Q000008:administration & dosage*; D004731:Endotoxins / Q000097:blood; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007408:Intestinal Absorption / Q000187:drug effects*; D007792:Lactulose / Q000493:pharmacokinetics; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012210:Rhamnose / Q000493:pharmacokinetics; D013395:Sucrose / Q000493:pharmacokinetics; D016559:Tacrolimus / Q000008:administration & dosage*
D004731:Endotoxins; D007166:Immunosuppressive Agents; D007792:Lactulose; D013395:Sucrose; D016572:Cyclosporine; D012210:Rhamnose; D016559:Tacrolimus