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01.04.2012 | Original Article

Pharmacokinetic and pharmacodynamic study on amrubicin and amrubicinol in Japanese patients with lung cancer

verfasst von: Yoshinori Makino, Noboru Yamamoto, Hitoshi Sato, Reiko Ando, Yasushi Goto, Chiharu Tanai, Hajime Asahina, Hiroshi Nokihara, Ikuo Sekine, Hideo Kunitoh, Yuichiro Ohe, Erika Sugiyama, Nobuaki Yokote, Tomohide Tamura, Hiroshi Yamamoto

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2012

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Abstract

Purpose

The pharmacokinetic (PK)–pharmacodynamic (PD) relationship of amrubicin and its active metabolite, amrubicinol, has only been evaluated using trough levels of these agents since the full PK profiles not yet been clarified so far. This study was performed to analyze the full PK profiles of amrubicin and amrubicinol and to evaluate their toxicity–PK relationships in Japanese patients.

Methods

Amrubicin (35–40 mg/m²) was administered to 21 lung cancer patients on days 1–3 every 3–4 weeks. Fourteen blood samples were obtained per patient over the course of 3 administration days. The plasma concentrations of amrubicin and amrubicinol were quantitated by HPLC, and the relationships between PK parameters of these compounds and hematological toxicities were evaluated.

Results

The overall PK profiles of amrubicin and amrubicinol were well characterized using a 3-compartment model and a 1-compartment model with a first-order metabolic process, respectively. The major toxicities were hematological. The clearance of amrubicinol was significantly correlated with grade 4 neutropenia (P = 0.01). The percentage decreases in the neutrophil count, hemoglobin level and platelet count were well correlated with the amrubicinol AUC.

Conclusion

The pharmacokinetic profiles of amrubicin and amrubicinol were clarified, and the subsequent PK–PD analyses indicate that the clearance of amrubicinol is the major determinant of neutropenia.

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Titel: Pharmacokinetic and pharmacodynamic study on amrubicin and amrubicinol in Japanese patients with lung cancer
verfasst von: Yoshinori Makino
Noboru Yamamoto
Hitoshi Sato
Reiko Ando
Yasushi Goto
Chiharu Tanai
Hajime Asahina
Hiroshi Nokihara
Ikuo Sekine
Hideo Kunitoh
Yuichiro Ohe
Erika Sugiyama
Nobuaki Yokote
Tomohide Tamura
Hiroshi Yamamoto
Publikationsdatum: 01.04.2012
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 4/2012
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-011-1768-8

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Pharmacokinetic and pharmacodynamic study on amrubicin and amrubicinol in Japanese patients with lung cancer