Temporal Decline in Sirolimus Elimination Immediately After Pancreatic Islet Transplantation

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Author(s)

    • 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

Abstract

  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>

Journal

  • Drug Metabolism and Pharmacokinetics

    Drug Metabolism and Pharmacokinetics 21(6), 492-500, 2006-12-25

    The Japanese Society for the Study of Xenobiotics

References:  29

Cited by:  3

Codes

  • NII Article ID (NAID)
    10018659035
  • NII NACSIS-CAT ID (NCID)
    AA1162652X
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    13474367
  • Data Source
    CJP  CJPref  J-STAGE 
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