Successful Telaprevir Treatment in Combination of Cyclosporine against Recurrence of Hepatitis C in the Japanese Liver Transplant Patients

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  • Kikuchi Mio
    Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Kyoto University Hospital Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital
  • Okuda Yuki
    Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Kyoto University Hospital
  • Ueda Yoshihide
    Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University
  • Nishioka Yuki
    Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital
  • Uesugi Miwa
    Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Kyoto University Hospital
  • Hashimoto Emina
    Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital
  • Takahashi Tamotsu
    Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital
  • Kawai Tomoki
    Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital
  • Hashi Sachiyo
    Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital
  • Shinke Haruka
    Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Kyoto University Hospital
  • Omura Tomohiro
    Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Kyoto University Hospital Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital
  • Yonezawa Atsushi
    Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Kyoto University Hospital Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital
  • Ito Takashi
    Division of Hepatobiliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University
  • Fujimoto Yasuhiro
    Division of Hepatobiliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University
  • Kaido Toshimi
    Division of Hepatobiliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University
  • Chiba Tsutomu
    Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University
  • Uemoto Shinji
    Division of Hepatobiliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University
  • Matsubara Kazuo
    Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Kyoto University Hospital Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital
  • Masuda Satohiro
    Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Kyoto University Hospital Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital

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Telaprevir (TVR) is a protease inhibitor used in combination with pegylated interferon alfa-2b and ribavirin for hepatitis C, and TVR strongly inhibits CYP3A4 and CYP3A5. We reported successful TVR treatment of liver transplant patients with recurrence of hepatitis C during receiving immunosuppressive therapy. Before initiation of triple therapy, all patients switched from tacrolimus to cyclosporine, which has a lower inhibitory effect on CYP3A4 and CYP3A5 than tacrolimus. To avoid graft failure, we measured the cyclosporine blood concentrations at 0, 2, and 6 h after administration to maintain the target level (150–200 ng/mL) within 1 week after initiation of TVR and adjusted the dose of cyclosporine. The dose of cyclosporine was decreased 0.24–0.40 fold in all patients after initiation of TVR treatment. In 3 patients, the dose of TVR was decreased two-thirds of starting dose because of adverse effects, including anorexia and skin rash. However, the HCV RNA level rapidly decreased to undetectable levels within 1 month. Furthermore, all patients completed the TVR therapy in 12 weeks and did not experience liver graft rejection. In addition, we found the rapid elimination of inhibitory effect of TVR on the disposition of cyclospirne in the all four cases and therefore, rapid increase in the dosage of cyclosporine would be required immediately after the end of TVR administration. These results suggest that frequent measurement of cyclosporine levels was important for successful TVR triple therapy and prevention of rejection.

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