Increased tacrolimus trough levels in association with severe diarrhea, a case report.
It is well known that during diarrhea episodes decreased cyclosporine and tacrolimus levels are often observed, usually requiring an increase in dose. An increase in tacrolimus trough levels is infrequently recognized as a potential cause of the adverse effect of severe diarrhea. Herein, we report the case of a renal transplant patient who displayed increased tacrolimus trough levels during an episode of gastroenteritis with severe diarrhea. The patient is 32-year-old male who received a renal transplant from his mother. Immunosuppression was initiated with tacrolimus in combination with mycophenolate mofetil and prednisone. The postoperative course was uneventful. The function of the transplanted kidney was normal. Eight months after transplantation he presented to our hospital with a history of high fever, abdominal pain, nausea and severe diarrhea. He was admitted with a diagnosis of enterocolitis of unknown etiology. The blood trough level of tacrolimus had increased from 6.7 ng/mL to 28.7 ng/mL after the onset of diarrhea. A therapeutic trough level of tacrolimus was reached 6 weeks after complete relief of diarrhea. Tacrolimus shows large variability in bioavailability after oral administration, both due to intestinal metabolism by cytochrome P450 (CYP3A4) and active secretion from enterocyte into intestinal lumen by P-glycoprotein. The epithelial cells of the intestine, may be destroyed abrogating P-glycoproteins during the course of enterocolitis, thereby increasing the levels of tacrolimus. It is recommended to monitor trough levels of tacrolimus during severe diarrhea of any nature to prevent tacrolimus-related complications.
Asano
T
T
Department of Urology, National Defense Medical College, Tokorozawa, Japan. otosani@me.ndmc.ac.jp
Nishimoto
K
K
Hayakawa
M
M
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003967:Diarrhea / Q000139:chemically induced*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000201:enzymology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D016559:Tacrolimus / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D016559:Tacrolimus