Successful telaprevir treatment in combination of cyclosporine against recurrence of hepatitis C in the Japanese liver transplant patients

Mio Kikuchi, Yuki Okuda, Yoshihide Ueda, Yuki Nishioka, Miwa Uesugi, Emina Hashimoto, Tamotsu Takahashi, Tomoki Kawai, Sachiyo Hashi, Haruka Shinke, Tomohiro Omura, Atsushi Yonezawa, Takashi Ito, Yasuhiro Fujimoto, Toshimi Kaido, Tsutomu Chiba, Shinji Uemoto, Kazuo Matsubara, Satohiro Masuda

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Abstract

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.

Original languageEnglish
Pages (from-to)417-423
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Volume37
Issue number3
DOIs
Publication statusPublished - Jan 1 2014

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Hepatitis C
Cyclosporine
Transplants
Recurrence
Liver
Cytochrome P-450 CYP3A
Therapeutics
Tacrolimus
telaprevir
Ribavirin
Graft Rejection
Anorexia
Immunosuppressive Agents
Exanthema
Protease Inhibitors
RNA

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

Successful telaprevir treatment in combination of cyclosporine against recurrence of hepatitis C in the Japanese liver transplant patients. / Kikuchi, Mio; Okuda, Yuki; Ueda, Yoshihide; Nishioka, Yuki; Uesugi, Miwa; Hashimoto, Emina; Takahashi, Tamotsu; Kawai, Tomoki; Hashi, Sachiyo; Shinke, Haruka; Omura, Tomohiro; Yonezawa, Atsushi; Ito, Takashi; Fujimoto, Yasuhiro; Kaido, Toshimi; Chiba, Tsutomu; Uemoto, Shinji; Matsubara, Kazuo; Masuda, Satohiro.

In: Biological and Pharmaceutical Bulletin, Vol. 37, No. 3, 01.01.2014, p. 417-423.

Research output: Contribution to journalArticle

Kikuchi, M, Okuda, Y, Ueda, Y, Nishioka, Y, Uesugi, M, Hashimoto, E, Takahashi, T, Kawai, T, Hashi, S, Shinke, H, Omura, T, Yonezawa, A, Ito, T, Fujimoto, Y, Kaido, T, Chiba, T, Uemoto, S, Matsubara, K & Masuda, S 2014, 'Successful telaprevir treatment in combination of cyclosporine against recurrence of hepatitis C in the Japanese liver transplant patients', Biological and Pharmaceutical Bulletin, vol. 37, no. 3, pp. 417-423. https://doi.org/10.1248/bpb.b13-00769
Kikuchi, Mio ; Okuda, Yuki ; Ueda, Yoshihide ; Nishioka, Yuki ; Uesugi, Miwa ; Hashimoto, Emina ; Takahashi, Tamotsu ; Kawai, Tomoki ; Hashi, Sachiyo ; Shinke, Haruka ; Omura, Tomohiro ; Yonezawa, Atsushi ; Ito, Takashi ; Fujimoto, Yasuhiro ; Kaido, Toshimi ; Chiba, Tsutomu ; Uemoto, Shinji ; Matsubara, Kazuo ; Masuda, Satohiro. / Successful telaprevir treatment in combination of cyclosporine against recurrence of hepatitis C in the Japanese liver transplant patients. In: Biological and Pharmaceutical Bulletin. 2014 ; Vol. 37, No. 3. pp. 417-423.
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AU - Uesugi, Miwa

AU - Hashimoto, Emina

AU - Takahashi, Tamotsu

AU - Kawai, Tomoki

AU - Hashi, Sachiyo

AU - Shinke, Haruka

AU - Omura, Tomohiro

AU - Yonezawa, Atsushi

AU - Ito, Takashi

AU - Fujimoto, Yasuhiro

AU - Kaido, Toshimi

AU - Chiba, Tsutomu

AU - Uemoto, Shinji

AU - Matsubara, Kazuo

AU - Masuda, Satohiro

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