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 language | English |
|---|---|
| Pages (from-to) | 81-87 |
| Number of pages | 7 |
| Journal | Cancer Treatment and Research Communications |
| Volume | 9 |
| DOIs | |
| Publication status | Published - Jan 1 2016 |
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Keywords
- Amrubicin
- Amrubicinol
- Dose adjustment
- Liver function test
- Pharmacokinetics
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=85034047038&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85034047038&partnerID=8YFLogxK
U2 - 10.1016/j.ctarc.2016.08.008
DO - 10.1016/j.ctarc.2016.08.008
M3 - Article
AN - SCOPUS:85034047038
VL - 9
SP - 81
EP - 87
JO - Cancer Treatment and Research Communications
JF - Cancer Treatment and Research Communications
SN - 2213-0896
ER -