1. Gene Polymorphism of Tacrolimus-Metabolizing Enzymes Associated With Impaired Absorption of Tacrolimus Following Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report.
- Author
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Matsuoka, S., Tsutsumi, Y., Kikuchi, R., Ito, S., and Teshima, T.
- Subjects
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HEMATOPOIETIC stem cell transplantation , *TACROLIMUS , *STEM cell transplantation , *ACUTE myeloid leukemia , *CYTOCHROME P-450 - Abstract
Abstract Objective To elucidate the mechanisms by which orally administered tacrolimus was not absorbed in a patient following allogeneic hematopoietic stem cell transplantation. Clinical Course A 17-year-old girl with acute myeloid leukemia underwent HLA-haploidentical peripheral blood stem cell transplantation following fludarabine, busulfan, and total-body irradiation. Graft-vs-host disease prophylaxis was post-transplant cyclophosphamide, followed by intravenous tacrolimus and mycophenolate mofetil. When tacrolimus was switched to oral administration, its blood level declined rapidly, resulting in development of acute graft-vs-host disease, which was ameliorated by switching back to intravenous administration. Methods/Results To elucidate if impaired tacrolimus absorption could be related to genetic polymorphism of tacrolimus-metabolizing enzymes, we analyzed gene polymorphisms of cytochrome P450 3A4, cytochrome P450 3A5, and multidrug resistance 1 (MDR1). The patient had wild-type cytochrome P450 3A4 (*1/*1) and variant-type cytochrome P450 3A5 (*3/*3), while MDR1 genes (2677A/G, 3435C/C) were wild-type. Conclusion Wild-type MDR1 gene product P-glycoprotein expressed in the intestine reduces drug absorption from the gastrointestinal tract and may have contributed to low blood levels of tacrolimus in this patient when tacrolimus was orally administered. Highlights • The patient's gene polymorphism of tacrolimus-metabolizing enzymes, especially MDR1, may be associated with insufficient absorption and lack of increase in blood level of tacrolimus when orally administered following allogeneic hematopoietic stem cell transplantation. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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