Temporal decline in sirolimus elimination immediately after pancreatic islet transplantation.

Eriko Sato, Masahiro Shimomura, Satohiro Masuda, Ikuko Yano, Toshiya Katsura, Shin ichi Matsumoto, Teru Okitsu, Yasuhiro Iwanaga, Hirofumi Noguchi, Hideo Nagata, Yukihide Yonekawa, Ken ichi Inui

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)492-500
Number of pages9
JournalDrug metabolism and pharmacokinetics
Volume21
Issue number6
DOIs
Publication statusPublished - Dec 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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