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Impact of cachexia on pharmacokinetic disposition of and clinical responses to oxycodone in cancer patients

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

Abstract

Purpose

Cancer cachexia is characterized by hypoalbuminemia and with the hepatic production of acute-phase proteins in response to malignant growth. The aim of this study was to evaluate the influence of cachexia on the pharmacokinetic disposition of and clinical responses to oxycodone in cancer patients.

Methods

Forty-seven Japanese patients receiving oxycodone extended-release tablets as a starting opioid for cancer pain were enrolled in this study. Cachexia was evaluated using the Glasgow Prognostic Score (GPS). Predose plasma concentrations of oxycodone and noroxycodone were determined at the titration dose.

Results

Seven patients had a GPS of 0, 21 a GPS of 1, and 19 had a GPS of 2. A higher GPS was significantly correlated with a higher oxycodone concentration and a lower concentration ratio of noroxycodone to oxycodone and significantly associated with a lower incidence of dose escalation and a higher incidence of central adverse reactions. Serum albumin, but not α1-acid glycoprotein and C-reactive protein, was inversely correlated with the free fraction of oxycodone. Serum albumin concentration was significantly associated with the incidence of dose escalation. In contrast, the free fraction of oxycodone and acute-phase proteins were not related to the clinical responses.

Conclusions

Cachexia had an effect on oxycodone metabolism and the clinical responses to oxycodone. The observed reduction in serum albumin concentration was associated with dose escalation. These findings suggest that cachexia affects the clinical responses to oxycodone through metabolic and nutritional disorders in cancer patients.

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Acknowledgments

This work was supported by a Grant-in-Aid for Scientific Research (C) from the Japanese Ministry of Education, Culture, Sports, Science and Technology (grant number 21590155).

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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

    Takafumi Naito, Masaki Tashiro, Keisuke Yamamoto & Junichi Kawakami

  2. Department of Clinical Pharmaceutics and Pharmacy Practice, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka City, Shizuoka, Japan

    Masaki Tashiro, Keisuke Yamamoto & Yoshiyuki Kagawa

  3. Oncology Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan

    Kazunori Ohnishi

Authors
  1. Takafumi Naito
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  2. Masaki Tashiro
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  3. Keisuke Yamamoto
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  4. Kazunori Ohnishi
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  5. Yoshiyuki Kagawa
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  6. Junichi Kawakami
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Correspondence to Junichi Kawakami.

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Naito, T., Tashiro, M., Yamamoto, K. et al. Impact of cachexia on pharmacokinetic disposition of and clinical responses to oxycodone in cancer patients. Eur J Clin Pharmacol 68, 1411–1418 (2012). https://doi.org/10.1007/s00228-012-1266-x

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  • DOI: https://doi.org/10.1007/s00228-012-1266-x

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