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. (Liver Transpl 2003;9:484-488.) D uring the last decade, an increasing number of subjects underwent orthotopic liver transplantation (OLT). 1 In Europe, the average survival rate 1 year after OLT currently is over 80%, and morbidity and mortality rates after transplantation are receiving increasing attention. 1 Infections, neoplasms and autoimmune disease, and a higher risk of hypertension and lipid abnormalities usually are observed after OLT, and all can negatively affect the outcome of the transplant. 2,3 Most of the metabolic alterations observed after OLT likely are associated with the use of immunosuppressive drugs, and various side effects have been reported during chronic therapy with cyclosporine (CsA) and tacrolimus (FK506). 4,5 During immunosuppressive and cytotoxic therapy, the intestinal epithelium can lose its barrier function. 6,7 This function can be evaluated in vivo by tests based on permeability of small intestine to sugar probes such as lactulose (Lacl) and rhamnose (L-Rh), administered orally and recovered in urine. 8 The ratio between urinary Lacl and L-Rh has been used to evaluate altered intestinal permeability in conditions such as immunodepression, 9,10 viral gastroenteritis, 11,12 coeliac disease, 13 and Crohn's disease. 14 In these conditions, the increased permeation of macromolecules through the intestinal wall takes place generally through the paracellular pathway and may be associated with high levels of plasmatic endotoxins. 15,16 FK506 has been reported to i...
