Temporal Decline in Sirolimus Elimination Immediately After Pancreatic Islet Transplantation

• SATO Eriko

  Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University

• SHIMOMURA Masahiro

  Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University

• MASUDA Satohiro

  Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University

• YANO Ikuko

  Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University

• KATSURA Toshiya

  Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University

• MATSUMOTO Shin-ichi

  Department of Transplantation and Immunology, Graduate School of Medicine, Kyoto University

• OKITSU Teru

  Department of Transplantation and Immunology, Graduate School of Medicine, Kyoto University

• IWANAGA Yasuhiro

  Department of Transplantation and Immunology, Graduate School of Medicine, Kyoto University

• NOGUCHI Hirofumi

  Department of Transplantation and Immunology, Graduate School of Medicine, Kyoto University

• NAGATA Hideo

  Department of Transplantation and Immunology, Graduate School of Medicine, Kyoto University

• YONEKAWA Yukihide

  Department of Transplantation and Immunology, Graduate School of Medicine, Kyoto University

• INUI Ken-ichi

  Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University

抄録

  Pancreatic islet transplantation is a curable treatment for type 1 diabetes and has been put into practice in various countries. In this study, we analyzed the pharmacokinetic characteristics of sirolimus and tacrolimus in six Japanese patients with pancreatic islet transplants immediately after surgery, and monitored efficacy and toxicity. The patients were treated with immunosuppressive therapy based on the Edmonton protocol, that is, sirolimus and low-dose tacrolimus. Pharmacokinetic analyses were performed using the nonlinear mixed-effects modeling program NONMEM. Large inter- and intra-individual variability was observed in the pharmacokinetics of sirolimus and tacrolimus. A model with increased apparent clearance in the postoperative period explained well the intra-individual variability in the pharmacokinetics of both drugs. The most frequent drug-induced toxicity was a decrease in the white blood cell count, and two of six patients required the administration of granulocyte colony-stimulating factor. Clinical laboratory tests immediately before the transplantation and cytochrome P450 3A5 genotype were not related to the high blood concentrations of sirolimus after the loading dose. From these results, the apparent clearance of sirolimus and tacrolimus might temporally decline immediately after pancreatic islet transplantation. A high trough concentration of sirolimus might increase the risk of hematological toxicy, and adjustment of the dosage for immunosuppressive treatment will be necessary in Japanese patients.<br>

収録刊行物

• Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ

  Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ 21 (6), 492-500, 2006

  日本薬物動態学会

キーワード

• tacrolimus
• pharmacokinetics
• CYP3A5
• HPLC/UV
• LC/MS/MS
• diabetes

詳細情報

• CRID: 1390282680156930432
• NII論文ID: 10018659035
• NII書誌ID: AA1162652X
• DOI: 10.2133/dmpk.21.492
• ISSN: 18800920
• ISSN: 13474367
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715307229?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715307229?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2007201993
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可