Pharmacokinetics of amrubicin in lung cancer patients with impaired hepatic function

Shinichiro Ryuge, Noriyuki Masuda, Nobuyuki Yamamoto, Toshiaki Takahashi, Haruyasu Murakami, Koji Takeda, Haruko Daga, Kimio Yonesaka, Hiroshi Tsukuda, Kazuhiko Nakagawa, Kaoru Tanaka, Katsuyuki Kiura, Nagio Takigawa, Toyoaki Hida, Takashi Seto, Masanori Yokoba, Shinzoh Kudoh, Takeshi Takagaki, Kazushige Shono, Hideo KitagawaTakeshi Kurihara, Masahiro Fukuoka

Research output: Contribution to journalArticle

Abstract

Objective The pharmacokinetics of amrubicin in patients with impaired hepatic function have not been reported. The aim of this study was to compare the pharmacokinetics of amrubicin and its major metabolite, amrubicinol, and to assess the safety of amrubicin in lung cancer patients with impaired hepatic function and those with normal hepatic function. Materials and methods Five patients with impaired hepatic function (arm I) and 10 patients with normal hepatic function (arm N) with small or non-small cell lung carcinoma were enrolled. Liquid chromatography with tandem mass spectrometry was used to determine the amrubicin and amrubicinol concentrations. Pharmacokinetic parameters were estimated by non-compartmental analysis. Results The terminal half-lives of amrubicin and amrubicinol in whole blood and plasma were slightly longer in arm I than in arm N. The area under the concentration–time curve (AUC0–24h) values of amrubicin in plasma and AUC0–120h of amrubicinol in whole blood in arm I were not larger than those in arm N because of dose adjustments based on prior treatment history and baseline values of total bilirubin, aspartate aminotransferase and alanine aminotransferase. The dose-normalized AUCs (dose 40 mg/m2) of amrubicin and amrubicinol in arm I were slightly larger than those in arm N. There were two deaths in arm I, one related to disease progression and one from an unknown cause. Conclusion If an adjusted dose of amrubicin is used in patients with impaired hepatic function, the exposure of amrubicin and amrubicinol would be within the range of variation observed in patients with normal hepatic function.

Original languageEnglish
Pages (from-to)81-87
Number of pages7
JournalCancer Treatment and Research Communications
Volume9
DOIs
Publication statusPublished - Jan 1 2016

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Lung Neoplasms
Pharmacokinetics
Liver
Area Under Curve
amrubicin
Aspartate Aminotransferases
Tandem Mass Spectrometry
Alanine Transaminase
Bilirubin
Non-Small Cell Lung Carcinoma
Liquid Chromatography
Disease Progression
amrubicinol
History
Safety

Keywords

  • Amrubicin
  • Amrubicinol
  • Dose adjustment
  • Liver function test
  • Pharmacokinetics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ryuge, S., Masuda, N., Yamamoto, N., Takahashi, T., Murakami, H., Takeda, K., ... Fukuoka, M. (2016). Pharmacokinetics of amrubicin in lung cancer patients with impaired hepatic function. Cancer Treatment and Research Communications, 9, 81-87. https://doi.org/10.1016/j.ctarc.2016.08.008

Pharmacokinetics of amrubicin in lung cancer patients with impaired hepatic function. / Ryuge, Shinichiro; Masuda, Noriyuki; Yamamoto, Nobuyuki; Takahashi, Toshiaki; Murakami, Haruyasu; Takeda, Koji; Daga, Haruko; Yonesaka, Kimio; Tsukuda, Hiroshi; Nakagawa, Kazuhiko; Tanaka, Kaoru; Kiura, Katsuyuki; Takigawa, Nagio; Hida, Toyoaki; Seto, Takashi; Yokoba, Masanori; Kudoh, Shinzoh; Takagaki, Takeshi; Shono, Kazushige; Kitagawa, Hideo; Kurihara, Takeshi; Fukuoka, Masahiro.

In: Cancer Treatment and Research Communications, Vol. 9, 01.01.2016, p. 81-87.

Research output: Contribution to journalArticle

Ryuge, S, Masuda, N, Yamamoto, N, Takahashi, T, Murakami, H, Takeda, K, Daga, H, Yonesaka, K, Tsukuda, H, Nakagawa, K, Tanaka, K, Kiura, K, Takigawa, N, Hida, T, Seto, T, Yokoba, M, Kudoh, S, Takagaki, T, Shono, K, Kitagawa, H, Kurihara, T & Fukuoka, M 2016, 'Pharmacokinetics of amrubicin in lung cancer patients with impaired hepatic function', Cancer Treatment and Research Communications, vol. 9, pp. 81-87. https://doi.org/10.1016/j.ctarc.2016.08.008
Ryuge, Shinichiro ; Masuda, Noriyuki ; Yamamoto, Nobuyuki ; Takahashi, Toshiaki ; Murakami, Haruyasu ; Takeda, Koji ; Daga, Haruko ; Yonesaka, Kimio ; Tsukuda, Hiroshi ; Nakagawa, Kazuhiko ; Tanaka, Kaoru ; Kiura, Katsuyuki ; Takigawa, Nagio ; Hida, Toyoaki ; Seto, Takashi ; Yokoba, Masanori ; Kudoh, Shinzoh ; Takagaki, Takeshi ; Shono, Kazushige ; Kitagawa, Hideo ; Kurihara, Takeshi ; Fukuoka, Masahiro. / Pharmacokinetics of amrubicin in lung cancer patients with impaired hepatic function. In: Cancer Treatment and Research Communications. 2016 ; Vol. 9. pp. 81-87.
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abstract = "Objective The pharmacokinetics of amrubicin in patients with impaired hepatic function have not been reported. The aim of this study was to compare the pharmacokinetics of amrubicin and its major metabolite, amrubicinol, and to assess the safety of amrubicin in lung cancer patients with impaired hepatic function and those with normal hepatic function. Materials and methods Five patients with impaired hepatic function (arm I) and 10 patients with normal hepatic function (arm N) with small or non-small cell lung carcinoma were enrolled. Liquid chromatography with tandem mass spectrometry was used to determine the amrubicin and amrubicinol concentrations. Pharmacokinetic parameters were estimated by non-compartmental analysis. Results The terminal half-lives of amrubicin and amrubicinol in whole blood and plasma were slightly longer in arm I than in arm N. The area under the concentration–time curve (AUC0–24h) values of amrubicin in plasma and AUC0–120h of amrubicinol in whole blood in arm I were not larger than those in arm N because of dose adjustments based on prior treatment history and baseline values of total bilirubin, aspartate aminotransferase and alanine aminotransferase. The dose-normalized AUCs (dose 40 mg/m2) of amrubicin and amrubicinol in arm I were slightly larger than those in arm N. There were two deaths in arm I, one related to disease progression and one from an unknown cause. Conclusion If an adjusted dose of amrubicin is used in patients with impaired hepatic function, the exposure of amrubicin and amrubicinol would be within the range of variation observed in patients with normal hepatic function.",
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T1 - Pharmacokinetics of amrubicin in lung cancer patients with impaired hepatic function

AU - Ryuge, Shinichiro

AU - Masuda, Noriyuki

AU - Yamamoto, Nobuyuki

AU - Takahashi, Toshiaki

AU - Murakami, Haruyasu

AU - Takeda, Koji

AU - Daga, Haruko

AU - Yonesaka, Kimio

AU - Tsukuda, Hiroshi

AU - Nakagawa, Kazuhiko

AU - Tanaka, Kaoru

AU - Kiura, Katsuyuki

AU - Takigawa, Nagio

AU - Hida, Toyoaki

AU - Seto, Takashi

AU - Yokoba, Masanori

AU - Kudoh, Shinzoh

AU - Takagaki, Takeshi

AU - Shono, Kazushige

AU - Kitagawa, Hideo

AU - Kurihara, Takeshi

AU - Fukuoka, Masahiro

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Objective The pharmacokinetics of amrubicin in patients with impaired hepatic function have not been reported. The aim of this study was to compare the pharmacokinetics of amrubicin and its major metabolite, amrubicinol, and to assess the safety of amrubicin in lung cancer patients with impaired hepatic function and those with normal hepatic function. Materials and methods Five patients with impaired hepatic function (arm I) and 10 patients with normal hepatic function (arm N) with small or non-small cell lung carcinoma were enrolled. Liquid chromatography with tandem mass spectrometry was used to determine the amrubicin and amrubicinol concentrations. Pharmacokinetic parameters were estimated by non-compartmental analysis. Results The terminal half-lives of amrubicin and amrubicinol in whole blood and plasma were slightly longer in arm I than in arm N. The area under the concentration–time curve (AUC0–24h) values of amrubicin in plasma and AUC0–120h of amrubicinol in whole blood in arm I were not larger than those in arm N because of dose adjustments based on prior treatment history and baseline values of total bilirubin, aspartate aminotransferase and alanine aminotransferase. The dose-normalized AUCs (dose 40 mg/m2) of amrubicin and amrubicinol in arm I were slightly larger than those in arm N. There were two deaths in arm I, one related to disease progression and one from an unknown cause. Conclusion If an adjusted dose of amrubicin is used in patients with impaired hepatic function, the exposure of amrubicin and amrubicinol would be within the range of variation observed in patients with normal hepatic function.

AB - Objective The pharmacokinetics of amrubicin in patients with impaired hepatic function have not been reported. The aim of this study was to compare the pharmacokinetics of amrubicin and its major metabolite, amrubicinol, and to assess the safety of amrubicin in lung cancer patients with impaired hepatic function and those with normal hepatic function. Materials and methods Five patients with impaired hepatic function (arm I) and 10 patients with normal hepatic function (arm N) with small or non-small cell lung carcinoma were enrolled. Liquid chromatography with tandem mass spectrometry was used to determine the amrubicin and amrubicinol concentrations. Pharmacokinetic parameters were estimated by non-compartmental analysis. Results The terminal half-lives of amrubicin and amrubicinol in whole blood and plasma were slightly longer in arm I than in arm N. The area under the concentration–time curve (AUC0–24h) values of amrubicin in plasma and AUC0–120h of amrubicinol in whole blood in arm I were not larger than those in arm N because of dose adjustments based on prior treatment history and baseline values of total bilirubin, aspartate aminotransferase and alanine aminotransferase. The dose-normalized AUCs (dose 40 mg/m2) of amrubicin and amrubicinol in arm I were slightly larger than those in arm N. There were two deaths in arm I, one related to disease progression and one from an unknown cause. Conclusion If an adjusted dose of amrubicin is used in patients with impaired hepatic function, the exposure of amrubicin and amrubicinol would be within the range of variation observed in patients with normal hepatic function.

KW - Amrubicin

KW - Amrubicinol

KW - Dose adjustment

KW - Liver function test

KW - Pharmacokinetics

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