The influence of commonly used immunosuppressive drugs on the small bowel functions - a comparative experimental study.
BACKGROUND
Gastrointestinal side effects of immunosuppressive drugs have got a high importance in clinical practice. The aim of this basic experimental study was to characterize the direct and immediate influence of seven commonly used immunosuppressive drugs on the small bowel functions. Therefore, the influence of ciclosporin A, tacrolimus, mycophenolate mofetil, enteric coated MPA, sirolimus, everolimus and FTY720 on-glucose absorption (I-GLU), chloride secretion (I-CHL), and barrier function (I-BAR) was investigated.<br />


METHODS
Jejunum of Wistar rats was mounted into modified Ussing-chambers and thereafter incubated with a low (therapeutic) or high (toxic) concentration of immunosuppressive drugs for one hour. I-GLU was measured by 3-O-methyl-D-glucopyranose kinetics. I-CHL was assessed through basal, bumetanide inhibited and theophylline + PgE(2 )activated short circuit current difference. I-BAR was assessed by transepithelial resistance and( 3)H-Lactulose-Flux.<br />


RESULTS
No differences were observed within the analyzed parameters whether immunosuppressive drugs were added from mucosal or serosal intestine side. The glucose absorption was not influenced by any of the analyzed immunosuppressive drugs. The small intestine barrier function was diminished by everolimus in the toxic group only. Only mycophenolate mofetil and EC-MPA decreased chloride secretion in the toxic concentration. None of the analyzed drugs increased chloride secretion.<br />


CONCLUSIONS
In conclusion, the analyzed immunosuppressive drugs had no direct and immediate influence on gastrointestinal function in therapeutic concentrations. However, toxic concentrations of mycophenolate mofetil, enteric coated MPA, and everolimus might be of importance for local effects on small bowel function due to oral application.<br /> <br /> <br />
Malinowski
Maciej
M
Department of General, Visceral, and Transplantation Surgery, University Hospital Charité, Berlin, Germany.
Martus
Peter
P
Neuhaus
Peter
P
Stockmann
Martin
M
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D000068338:Everolimus; D000068876:Fingolimod Hydrochloride; D005769:Gastrointestinal Motility / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects*; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D011409:Propylene Glycols / Q000494:pharmacology; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D016572:Cyclosporine; D000068338:Everolimus; D000068876:Fingolimod Hydrochloride; D009173:Mycophenolic Acid; D013110:Sphingosine; D020123:Sirolimus; D016559:Tacrolimus