title: Phase I clinical trial of olprinone in liver surgery.
abstract: OBJECTIVE
  Post-hepatectomy liver failure is one of the most serious complications liver surgeons must overcome. We previously examined olprinone, a selective phosphodiesterase III inhibitor, and demonstrated its hepatoprotective effects in rats and pigs. We herein report the results of a phase I clinical trial of olprinone in liver surgery (UMIN000004975).
  
  
  METHODS
  Twenty-three patients who underwent hepatectomy between 2011 and 2015 were prospectively registered. In the first 6 cases, olprinone (0.1 μg/kg/min) was administered for 24 h from the start of surgery. In the remaining 17 cases, olprinone (0.05 μg/kg/min) was administered from the start of surgery until just before the transection of the liver parenchyma. The primary endpoint was safety, and the secondary endpoint was efficacy. For the evaluation of efficacy, the incidence of post-hepatectomy liver failure in 20 hepatocellular carcinoma patients was externally compared with 20 propensity score-matched patients.
  
  
  RESULTS
  No intraoperative side effects were observed, and the morbidity rates in the analyzed cohorts were acceptable. The rate of post-hepatectomy liver failure frequency tended to be lower in the olprinone group.
  
  
  CONCLUSIONS
  The safety of olprinone in liver surgery was confirmed. The efficacy of olprinone will be re-evaluated in clinical trials.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fuji
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. shatano@hyo-med.ac.jp.|Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan. shatano@hyo-med.ac.jp.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Hatano
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kohta
authors.initials: K
authors.lastname: Iguchi
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Yamanaka
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoh
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Ikeno
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Seo
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Taura
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yasuchika
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Anesthesia, Tenri Hospital, Tenri, Japan.
authors.forename: Hisanari
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Science, Niigata, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Science, Niigata, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ueno
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000601:surgery; D015331:Cohort Studies; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D015994:Incidence; D017093:Liver Failure / Q000453:epidemiology / Q000517:prevention & control*; D008113:Liver Neoplasms / Q000601:surgery; D008297:Male; D008875:Middle Aged; D058987:Phosphodiesterase 3 Inhibitors / Q000008:administration & dosage*; D011183:Postoperative Complications / Q000453:epidemiology / Q000517:prevention & control*; D057216:Propensity Score; D011728:Pyridones / Q000008:administration & dosage*; D057170:Translational Research, Biomedical; D016896:Treatment Outcome
chemical_list: D007093:Imidazoles; D058987:Phosphodiesterase 3 Inhibitors; D011728:Pyridones; C059498:olprinone
keywords: Olprinone; Phase I clinical trial; Post-hepatectomy liver failure; Selective phosphodiesterase III inhibitor; Translational research