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Relationships between oxycodone pharmacokinetics, central symptoms, and serum interleukin-6 in cachectic cancer patients

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Elevated serum proinflammatory cytokines are associated with the reduction of cytochrome P450 enzyme (CYP) activity. This study aimed to evaluate the oxycodone pharmacokinetics, central symptoms, and serum proinflammatory cytokines based on cachexia stage in cancer patients.

Methods

Forty-seven cancer patients receiving extended-release oxycodone were enrolled. Predose plasma concentrations of oxycodone and its metabolites were normalized with the daily dose and body weight. The central symptoms and serum level of proinflammatory cytokines were investigated at each cachexia stage.

Results

The plasma concentrations of oxycodone in patients with cachexia and refractory cachexia were significantly higher than that in patients with precachexia. The metabolic ratio to noroxycodone in patients with cachexia was significantly lower than that in patients with precachexia. The patients with a higher cachexia stage had a higher serum level of interleukin-6 (IL-6), but not tumor necrosis factor-α and interleukin-1β. The serum IL-6 level was correlated with the plasma concentration of oxycodone and inversely with the metabolic ratio to noroxycodone. The incidence of somnolence was not associated with the plasma oxycodone concentration. In contrast, the cachexia stage and its associated serum IL-6 level were correlated with the incidence of somnolence.

Conclusions

Cancer cachexia raised the plasma exposure of oxycodone through the reduction of CYP3A metabolic pathway. The reduction of CYP3A in cachectic cancer patients was associated with an elevation of serum IL-6. Although cachectic cancer patients with higher serum IL-6 levels had the symptom of somnolence, the alterations in oxycodone pharmacokinetics were not related to the incidence of symptom.

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Acknowledgments

This work was supported by JSPS KAKENHI grant numbers 26460194 and 26927005.

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Authors and Affiliations

  1. Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan

    Hikaru Sato, Takafumi Naito, Takuya Ishida & Junichi Kawakami

Authors
  1. Hikaru Sato
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  2. Takafumi Naito
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  3. Takuya Ishida
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  4. Junichi Kawakami
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Corresponding author

Correspondence to Takafumi Naito.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was performed in accordance with the Declaration of Helsinki and its amendments, and the protocol (25-306) was approved by the Ethics Committee of Hamamatsu University School of Medicine. The patients received information about the scientific aim of the study and each patient provided written informed consent.

Informed consent

All the patients gave their written consent to their participation in the study.

Funding

This work was supported by JSPS KAKENHI Grant Numbers 26460194 and 26927005.

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Sato, H., Naito, T., Ishida, T. et al. Relationships between oxycodone pharmacokinetics, central symptoms, and serum interleukin-6 in cachectic cancer patients. Eur J Clin Pharmacol 72, 1463–1470 (2016). https://doi.org/10.1007/s00228-016-2116-z

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  • DOI: https://doi.org/10.1007/s00228-016-2116-z

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