HPLC analysis and pharmacokinetic characteristics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, in rats and beagle dogs.

Abstract

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 (0.02 microg/ml) at 4 and 8 h after i.v. administration in rats at doses of 2 and 10 mg/kg, respectively (t(1/2,alpha) and t(1/2,beta) 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.

Statistics

0200400'06'07'08'09'10'11'12'13'14'15'16'17
Citations per Year

247 Citations

Semantic Scholar estimates that this publication has 247 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Yoo2005HPLCAA, title={HPLC analysis and pharmacokinetic characteristics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, in rats and beagle dogs.}, author={Bo-im Yoo and Kwang Bok Ahan and Min Hee Kang and Dong-Cheul Moon and Oh-Seung Kwon and Hong Sub Lee and Jung Su Ryu and Tae Yong Kim and Sukgil Song and Youn Bok Chung}, journal={Biological & pharmaceutical bulletin}, year={2005}, volume={28 4}, pages={688-93} }