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The Impact of Total Gastrectomy on Pharmacokinetics in Kidney Transplant Immunosuppressive Drug Regimes: A Case Study

Chen, Lucy BScPhm1; Liberatore, Lisa BScPhm1; Chin, Tom PharmD2; Walker, Scott MScPhm3; Fanous, Helen PharmD1; Nash, Michelle M MSc1; Rapi, Lindita BScM1; Huckle, Jennie RN1; Zaltzman, Jeffrey S MD, MSc1; Prasad, G V Ramesh MBBS, MSc, MA1

doi: 10.1097/TP.0000000000001507
Original Clinical Science-General

Background: Ensuring reliable gastrointestinal drug absorption of orally administered immunosuppressive medications posttransplant is critical to ensuring graft survival.

Methods: A 66-year-old man of East Asian origin with a previous total gastrectomy was evaluated for living donor kidney transplantation. Pretransplant pharmacokinetic testing was performed to determine the most appropriate posttransplant medication strategy. The Gastrointestinal Quality of Life Index and Gastrointestinal Rating Scale questionnaires were administered to gauge immunosuppressive medication-related side effects in the absence of a stomach.

Results: The patient's ability to absorb cyclosporin, tacrolimus (Tac), enteric-coated mycophenolate sodium (EC-MPS) and sirolimus (SRL) in oral dosage forms was well-preserved. Compared to nongastrectomy reference populations, the rate and extent of absorption of SRL and mycophenolic acid from EC-MPS were similar. The absorption of Tac and cyclosporin was greater than expected. Mycophenolate mofetil did not provide mycophenolic acid absorption as well as EC-MPS. The patient had worsened gastrointestinal symptoms with mycophenolate mofetil or EC-MPS in combination with Tac and cyclosporin, but this was not seen with isolated SRL.

Conclusions: This case demonstrates that commonly used postkidney transplantation immunosuppressive regimes may be prescribed after total gastrectomy as long as their limitations are noted.

This study of a patient with total gastrectomy shows the absorption of tacrolimus and cyclosporine was greater than expected, with sirolimus as expected and mycophenolate mofetil (MMF) did not provide absorption as well as enteric coated-mycophenolic acid (EC-MPA).

1 Renal Transplant Program, St. Michael’s Hospital, Toronto, ON, Canada.

2 Department of Pharmacy, St. Michael’s Hospital, Toronto, ON, Canada.

3 Department of Pharmacy, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Received 11 May 2016. Revision received 22 August 2016.

Accepted 10 September 2016.

This study was supported by an unrestricted education grant from Novartis Canada.

The authors declare no conflicts of interest.

L.C. participated in data analysis and interpretation, and drafting the article. L.L. participated in the conception and design of the study, study coordination, data analysis, and interpretation. T.C. participated in the conception and design of the study. S.W. participated in the data analysis and interpretation. H.F. participated in the data collection, study coordination, data analysis, and interpretation. M.M.N. participated in the design of the study, study coordination and management, and critical revision of the article. L.R. participated in the critical revision of the article. J.H. participated in the study coordination and data collection. J.S.Z. participated in the final approval of the article. G.V.R.P. participated in the conception and design of the study, data collection, data analysis and interpretation, critical revision of the article.

Correspondence: G.V. Ramesh Prasad, MBBS, MSc, MA, Renal Transplant Program, St. Michael's Hospital 61 Queen St E, 9th Floor, Toronto, ON M5C 2T2, Canada. (prasadr@smh.ca).

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