HPLC Analysis and Pharmacokinetic Characteristics of 11-Hydroxyaclacinomycin X (ID-6105), a Novel Anthracycline, in Rats and Beagle Dogs(Biopharmacy)

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概要

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• We investigated the pharmacokinetic characteristics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, after intravenous (i.v.) bolus administration in rats and beagle dogs. We developed an HPLC-based method to analyze ID-6105 levels in plasma, bile, urine, feces, and tissue homogenates and validated the method in a pharmacokinetic study. The plasma concentration of ID-6105 decreased to below the quantifiable limit (0.02μg/ml) at 4 and 8 h after i.v. administration in rats at doses of 2 and 10 mg/kg, respectively (t_<1/2, α> and t_<1/2, β> of 0.78 and 17.8 min at a dose of 2 mg/kg, 0.91 and 176 min at a dose of 10 mg/kg, respectively). The AUC increased with nonlinear pharmacokinetics following the dosage increase from 2 to 10 mg/kg in rats, while the pharmacokinetics were not significantly altered in beagle dogs following a dosage increase from 0.5 to 2.5 mg/kg. Of the various tissues tested, ID-6105 was mainly distributed in the lung, spleen, kidney, adrenal gland, and liver after i.v. bolus administration. ID-6105 levels in the lung or kidney 2 h after i.v. bolus administration were comparable to the initial plasma concentration. However, the ID-6105 concentrations in various tissues 48 h after i.v. bolus administration became too small to measure. The cumulative amounts of ID-6105 found in the bile 48 h after the administration of 2 and 10 mg/kg were calculated to be 26.7 and 18.5% of the initial dose, respectively. The corresponding values in the urine 72 h after i.v. administration were 4.33 and 3.07% of the initial dose, suggesting that ID-6105 is mostly excreted in the bile. In conclusion, our observations indicate that ID-6105 was rapidly cleared from the blood and transferred to tissues such as the lung, spleen, kidney, and liver 2 h after i.v. bolus administration. Moreover, the majority of ID-6105 appears to be excreted in the bile by 24 h after i.v. bolus administration.

• 公益社団法人日本薬学会の論文
• 2005-04-01

著者

• KANG Min

  National Nanofab Center

• Yoo Bo-im

  韓国

• Yoo Bo

  National Research Laboratory (nrl) Of Pk

• Yoo Bo-im

  National Research Laboratory (nrl) Of Pk/pd Biotechnology Research Institute College Of Pharmacy Chu

• Moon Dong

  Pd Biotechnology Research Institute College Of Pharmacy Chungbuk National University

• AHAN Kwang

  PD, Biotechnology Research Institute, College of Pharmacy, Chungbuk National University

• MOON Dong

  PD, Biotechnology Research Institute, College of Pharmacy, Chungbuk National University

• KWON Oh

  National Research Laboratory (NRL) of PK

• LEE Hong

  PD, Biotechnology Research Institute, College of Pharmacy, Chungbuk National University

• RYU Jung

  National Research Laboratory (NRL) of PK

• KIM Tae

  PD, Biotechnology Research Institute, College of Pharmacy, Chungbuk National University

• SONG Sukgil

  Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology

• CHUNG Youn

  Research Laboratories, ILDONG Pharmaceutical Co. Ltd.

• Chung Youn

  Research Laboratories Ildong Pharmaceutical Co. Ltd.

• Ahan Kwang

  Pd Biotechnology Research Institute College Of Pharmacy Chungbuk National University

• Lee Hong

  Pd Biotechnology Research Institute College Of Pharmacy Chungbuk National University

• Song Sukgil

  Bioanalysis And Biotransformation Research Center Korea Institute Of Science And Technology

• Kang Min

  National Research Laboratory (nrl) Of Pk

• Kim Tae

  Pd Biotechnology Research Institute College Of Pharmacy Chungbuk National University

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