title: Pharmacokinetics of amrubicin and its active metabolite amrubicinol in lung cancer patients.
abstract: Amrubicin, a synthetic 9-aminoanthracycline agent, was recently approved in Japan for treatment of small-cell lung cancer and non-small-cell lung cancer. Amrubicin is converted enzymatically to the C-13 hydroxy metabolite amrubicinol, which is active and possesses a cytotoxicity 10 to 100 times that of the parent drug. The purpose of this study was to characterize the pharmacokinetics of amrubicin and its active metabolite amrubicinol. Amrubicin was administered on days 1-3 in 16 patients with advanced lung cancer. The pharmacokinetics analysis of amrubicin and amrubicinol was performed by high-performance liquid chromatography. When 45 mg/m amrubicin was administered in a bolus injection once every 24 hours for 3 consecutive days, the areas under the curves (0 to 72 hours) for amrubicin and amrubicinol were 13,490 and 2585 ng . h/mL, respectively. The apparent total clearance (CLapp) of amrubicin was 15.4 L/h. The area-under-the-curve ratio of amrubicinol to amrubicin was 15.1 +/- 4.6% (mean +/- SD) at doses ranging from 30 to 45 mg/m. Interindividual variability in the enzymatic conversion of amrubicin to amrubicinol was small. In contrast, a large interindividual variability in the CLapp of amrubicin was observed (CV = 49.8%). The areas under the curves of amrubicin and amrubicinol seemed to be associated with the severity of hematologic toxicities. There is a possibility that monitoring of the plasma concentrations of amrubicin and amrubicinol may provide an efficient tool for establishing the optimal dosage of amrubicin in each patient.
authors.affiliation: Department of Pharmacy, Kumamoto University Hospital, Kumamoto 860-8556, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: Akinobu
authors.initials: A
authors.lastname: Hamada
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Ji-ichiro
authors.initials: J
authors.lastname: Sasaki
authors.forename: Eiji
authors.initials: E
authors.lastname: Moriyama
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kishi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Asumi
authors.initials: A
authors.lastname: Hira
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saito
mesh_terms: D000368:Aged; D018943:Anthracyclines / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D018943:Anthracyclines; C116173:amrubicinol; C055866:amrubicin