Yoo, BI Ahan, KB Kang, MH Moon, DC Kwon, OS Lee, HS Ryu, JS Kim, TY Song, S Chung, YB 2024-01-21T05:11:37Z 2024-01-21T05:11:37Z 2021-09-03 2005-04 0918-6158 https://pubs.kist.re.kr/handle/201004/136611 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 mu g/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. English PHARMACEUTICAL SOC JAPAN HPLC analysis and pharmacokinetic characteristics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, in rats and beagle dogs Article 10.1248/bpb.28.688 1 BIOLOGICAL & PHARMACEUTICAL BULLETIN, v.28, no.4, pp.688 - 693 BIOLOGICAL & PHARMACEUTICAL BULLETIN 28 4 688 693 N scie scopus 000228462800025 2-s2.0-21144433387 Pharmacology & Pharmacy Pharmacology & Pharmacy Article STREPTOMYCES-GALILAEUS ATCC-31133 AKLAVINONE 11-HYDROXYLASE GENE BLOCKED MUTANT ACLACINOMYCIN ANTIBIOTICS METABOLITES CAESIUS 11-hydroxyaclacinomycin X (ID-6105) pharmacokinetics HPLC tissue distribution excretion