title: Successful telaprevir treatment in combination of cyclosporine against recurrence of hepatitis C in the Japanese liver transplant patients.
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.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Kyoto University Hospital.
authors.forename: Mio
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Okuda
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Ueda
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nishioka
authors.forename: Miwa
authors.initials: M
authors.lastname: Uesugi
authors.forename: Emina
authors.initials: E
authors.lastname: Hashimoto
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Takahashi
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kawai
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Hashi
authors.forename: Haruka
authors.initials: H
authors.lastname: Shinke
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Omura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yonezawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Toshimi
authors.initials: T
authors.lastname: Kaido
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Matsubara
authors.forename: Satohiro
authors.initials: S
authors.lastname: Masuda
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016572:Cyclosporine / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects* / Q000601:surgery / Q000821:virology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012313:RNA / Q000378:metabolism; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D009842:Oligopeptides; D011480:Protease Inhibitors; D012313:RNA; C486464:telaprevir; D016572:Cyclosporine