Pharmacokinetics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, after i.v. bolus multiple administration in rats

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Title
Pharmacokinetics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, after i.v. bolus multiple administration in rats
Author(s)
B I Yoo; K B Ahan; M H Kang; O S Kwon; Young-Soo Hong; Jung Joon Lee; H S Lee; J S Ryu; T Y Kim; D C Moon; S Song; Y B Chung
Bibliographic Citation
Archives of Pharmacal Research, vol. 28, no. 4, pp. 476-482
Publication Year
2005
Abstract
We investigated the pharmacokinetics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, after intravenous (i.v.) bolus administration at a multiple dose every 24 h for 5 days in rats. To analyze ID-6105 levels in biological samples, we used an HPLC-based method which was validated in a pharmacokinetic study by suitable criteria. The concentrations of ID-6105 after the multiple administration for 5 days were not significantly different from the results after the single administration. The t1/2α, t 1/2β, Vdss, and CLt after the multiple administration were not significantly different from the values after the single administration. Moreover, the concentrations of ID-6105 1 min at day 1-5 after i.v. bolus multiple administration did not show the significant difference. of the various tissues, ID-6105 mainly distributed to the kidney, lung, spleen, adrenal gland, and liver after i.v. bolus multiple administration. ID-6105 concentrations in the kidney or lung 2 h after i.v. bolus administration were comparable to the plasma concentration shortly after i.v. bolus administration. However, the ID-6105 concentrations in various tissues 48 h after i.v. bolus administration decreased to low levels. ID-6105 was excreted largely in the bile after i.v. bolus multiple administration at the dose of 3 mg/kg. The amounts of ID-6105 found in the bile by 12 h or in the urine by 48 h after the administration were calculated to be 14.1% or 4.55% of the initial dose, respectively, indicating that ID-6105 is mostly excreted in the bile. In conclusion, ID-6105 was rapidly cleared from the blood and transferred to tissues, suggesting that ID-6105 might not be accumulated in the blood following i.v. bolus multiple dosages of 3 mg/kg every 24 h for 5 days. By 48 h after i.v. bolus administration, ID-6105 concentrations in various tissues had decreased to very low levels. The majority of ID-6105 appears to be excreted in the bile.
Keyword
11-Hydroxyaclacinomycin X (ID-6105)ExcretionMultiple administrationPharmacokineticsTissue distribution
ISSN
0253-6269
Publisher
Pharmaceutical Soc Korea
DOI
http://dx.doi.org/10.1007/BF02977679
Type
Article
Appears in Collections:
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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