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

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European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Abstract

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.

Methods

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.

Results

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].

Conclusion

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

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Authors and Affiliations

  1. Department of Pharmacy, NTT Medical Centre Tokyo, 5-9-22 Higashi-gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan

    Hirokazu Nakayama, Takao Orii & Toshiaki Kato

  2. Department of Pharmacotherapy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan

    Hirotoshi Echizen & Ryuichi Ogawa

Authors
  1. Hirokazu Nakayama
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  2. Hirotoshi Echizen
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  3. Ryuichi Ogawa
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  4. Takao Orii
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  5. Toshiaki Kato
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Corresponding author

Correspondence to Hirokazu Nakayama.

Ethics declarations

Funding

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.

Appendix

Appendix

Plasma phenobarbital clearance (L/kg/day) of patients at the entry of the study

No

Non-cancer patients

Cancer patients

Long-surviving

Short-surviving

1

0.100

0.092

0.069

2

0.065

0.102

0.098

3

0.082

0.149

0.114

4

0.066

0.106

0.105

5

0.099

0.097

0.061

6

0.098

0.092

0.060

7

0.071

0.122

0.057

8

0.096

0.082

0.083

9

0.068

0.103

0.084

10

0.096

0.100

0.057

11

0.090

0.083

 

12

0.135

0.089

 

13

0.153

0.101

 

14

0.137

0.104

 

15

0.097

0.115

 

16

0.148

0.103

 

17

0.109

0.095

 

18

0.163

0.093

 

19

0.165

0.086

 

20

0.109

0.116

 

21

0.083

0.100

 

22

0.126

0.109

 

23

0.161

0.112

 

24

0.117

0.084

 

25

0.111

  

26

0.106

  

27

0.101

  

28

0.117

  

29

0.147

  

30

0.083

  

31

0.126

  

32

0.226

  

33

0.081

  

34

0.118

  

35

0.076

  

36

0.067

  

37

0.103

  

38

0.141

  

39

0.060

  

40

0.117

  

41

0.152

  

42

0.094

  

43

0.111

  

44

0.104

  

Median (range)

0.105 (0.060‒0.226)*

0.100 (0.082‒0.149)*

0.076 (0.057‒0.114)

  1. *p < 0.05 compared with the short surviving cancer patients

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Nakayama, H., Echizen, H., Ogawa, R. et al. Reduced Clearance of Phenobarbital in Advanced Cancer Patients near the End of Life. Eur J Drug Metab Pharmacokinet 44, 77–82 (2019). https://doi.org/10.1007/s13318-018-0495-5

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  • DOI: https://doi.org/10.1007/s13318-018-0495-5

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