Reduced Clearance of Phenobarbital in Advanced Cancer Patients near the End of Life

  • Hirokazu NakayamaEmail author
  • Hirotoshi Echizen
  • Ryuichi Ogawa
  • Takao Orii
  • Toshiaki Kato
Original Research Article


Background and Objectives

Little is known about the pharmacokinetics of phenobarbital in terminally ill cancer patients. We investigated whether phenobarbital clearance alters depending on the length of survival.


We retrospectively reviewed the clinical, laboratory, and therapeutic drug monitoring (TDM) records of patients who received parenteral or oral phenobarbital for 21 consecutive days or longer between 2000 and 2016. Patients were divided into non-cancer and cancer groups. Cancer patients were further stratified according to the survival interval after TDM: those who survived > 3 months were classified as long-surviving and the remainders short-surviving cancer patients. Phenobarbital clearance (CLPB) was calculated at steady state. Multiple comparisons of median CLPB were conducted among the three groups.


Data were collected from 44 non-cancer patients and 34 cancer patients comprising 24 long-surviving and 10 short-surviving cancer patients. Among 10 short-surviving cancer patients, 4 had hepatic metastasis. Median CLPB (range) in short-surviving cancer patients [0.076 (0.057‒0.114) L/kg/day] was significantly (p < 0.05) lower than that in non-cancer patients [0.105 (0.060‒0.226) L/kg/day] and in long-surviving cancer patients [0.100 (0.082‒0.149) L/kg/day].


Terminally ill patients with advanced cancer may have reduced CLPB, thereby TDM is recommended for these patients particularly near the end of life.


Compliance with Ethical Standards


This research did not receive any specific grant from funding agencies in the public, commercial, or non-profitable organizations.

Conflict of interest

The authors declare no conflicts of interest.

Ethics approval

The protocol of the present study was approved by the Ethics Committee of NTT Medical Centre Tokyo (Reference No. 16-1319) prior to the study.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of PharmacyNTT Medical Centre TokyoTokyoJapan
  2. 2.Department of PharmacotherapyMeiji Pharmaceutical UniversityKiyoseJapan

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