title: Elevated portal vein drug levels of sirolimus and tacrolimus in islet transplant recipients: local immunosuppression or islet toxicity?
abstract: The recent success of islet transplantation using the Edmonton protocol involved the use of sirolimus, tacrolimus, and daclizumab for immunosuppression. Islets were infused into the portal circulation after transhepatic access. This protocol provided a unique opportunity to measure sirolimus and tacrolimus levels from the portal vein and compare them to systemic venous levels. A total of 11 portal venous samples with a corresponding peripheral venous sample were obtained from patients undergoing a first or second islet infusion and medication levels were obtained on both types of specimens. The portal-to-systemic drug level ratio ranged from 0.95 to 2.71 for sirolimus and 1.0 to 3.12 for tacrolimus. Given the potential toxicity of these agents to islets, the findings in this study may have implications for designing the next generation of immunosuppressive protocols for islet transplantation.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Niraj M
authors.initials: NM
authors.lastname: Desai
authors.forename: John A
authors.initials: JA
authors.lastname: Goss
authors.forename: Shaoping
authors.initials: S
authors.lastname: Deng
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Wolf
authors.forename: Eileen
authors.initials: E
authors.lastname: Markmann
authors.forename: Maral
authors.initials: M
authors.lastname: Palanjian
authors.forename: Angela P
authors.initials: AP
authors.lastname: Shock
authors.forename: Sue
authors.initials: S
authors.lastname: Feliciano
authors.forename: F Charles
authors.initials: FC
authors.lastname: Brunicardi
authors.forename: Clyde F
authors.initials: CF
authors.lastname: Barker
authors.forename: Ali
authors.initials: A
authors.lastname: Naji
authors.forename: James F
authors.initials: JF
authors.lastname: Markmann
mesh_terms: D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000473:pathology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D011168:Portal System; D011169:Portal Vein / Q000502:physiology*; D012044:Regression Analysis; D020123:Sirolimus / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus