title: Pharmacokinetic and pharmacodynamic study on amrubicin and amrubicinol in Japanese patients with lung cancer.
abstract: OBJECTIVE
  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/m(2)) 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmacy, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. ymakino@ncc.go.jp
authors: Yoshinori
authors: Y
authors: Makino
authors: Noboru
authors: N
authors: Yamamoto
authors: Hitoshi
authors: H
authors: Sato
authors: Reiko
authors: R
authors: Ando
authors: Yasushi
authors: Y
authors: Goto
authors: Chiharu
authors: C
authors: Tanai
authors: Hajime
authors: H
authors: Asahina
authors: Hiroshi
authors: H
authors: Nokihara
authors: Ikuo
authors: I
authors: Sekine
authors: Hideo
authors: H
authors: Kunitoh
authors: Yuichiro
authors: Y
authors: Ohe
authors: Erika
authors: E
authors: Sugiyama
authors: Nobuaki
authors: N
authors: Yokote
authors: Tomohide
authors: T
authors: Tamura
authors: Hiroshi
authors: H
authors: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D055752:Small Cell Lung Carcinoma / Q000097:blood / Q000188:drug therapy / Q000378:metabolism
chemical_list: D018943:Anthracyclines; C116173:amrubicinol; C055866:amrubicin