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Pharmacokinetics of 11-Hydroxyaclacinomycin X (ID-6105), a Novel Anthracycline, after i.v. Bolus Multiple Administration in Rats

Yoo Bo-Im    (National Research Laboratory (NRL) of PK/PD, Biotechnology Research Institute, College of Pharmacy, Chungbuk National University   ); Ahan Kwang Bok    (National Research Laboratory (NRL) of PK/PD, Biotechnology Research Institute, College of Pharmacy, Chungbuk National University   ); Kang Min Hee    (National Research Laboratory (NRL) of PK/PD, Biotechnology Research Institute, College of Pharmacy, Chungbuk National University   ); Kwon Oh-Seung    (Korea Institute of Science and Technology   ); Hong Young-Soo    (Korea Research Institute of Bioscience and Biotechnology   ); Lee Jung Joon    (Korea Research Institute of Bioscience and Biotechnology   ); Lee Hong Sub    (Research Laboratories, ILDONG Pharmaceutical Co. Ltd.   ); Ryu Jung Su    (Research Laboratories, ILDONG Pharmaceutical Co. Ltd.   ); Kim Tae Yong    (Research Laboratories, ILDONG Pharmaceutical Co. Ltd.   ); Moon Dong-Cheul    (National Research Laboratory (NRL) of PK/PD, Biotechnology Research Institute, College of Pharmacy, Chungbuk National University   ); Song Sukgil    (National Research Laboratory (NRL) of PK/PD, Biotechnology Research Institute, College of Pharmacy, Chungbuk National University   ); Chung Youn Bok    (National Resear  );
  • 초록

    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 $t_{1/2\alpha}, t_{l/2\beta}, V_{dss}, and CL_{t}$ 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.


  • 주제어

    11-Hydroxyaclacinomycin X (ID-6105) .   Pharmacokinetics .   Multiple administration .   Tissue distribution .   Excretion.  

  • 참고문헌 (14)

    1. Arcamone, F., Cassinelli, G., Fantini, G., Graein, A., Orezzi, P. Poli, C., and Spalla, C., Adriamycin, 14-hydroxy daunomycin, a new antitumor antibiotic from Streptomyces peucetius var. caesius. Biotechnol. Bioeng., 11, 1101-1110 (1969) 
    2. Myers, C. E., Miminaugh, E. G., Yeh, G. C., and Sinha, B. K., Biochemical mechanisms of tumor cell kill by anthracyclines, In Anthracycline and anthracenedione based anticancer agents. Ed. Lown J. W., Elsevier, Amsterdam, pp. 527-569 (1998) 
    3. Nakagawa, M., Furihata, K., Adachi, K., Seto, H., and Otake, N., The structure of a new anthracycline, cinerubicin X produced by a blocked mutant of Streptomyces violaceochromogenes. J. Antibiotics, 39, 1178-1179 (1986) 
    4. Oki, T., Kitamura, I., Matsuzawa, Y., Shibarmoto, N., Ogasawara, T., Yoshimoto, T., Inui, T., Naganawa, H., Takeuchi, T., and Umezawa, H., Antitumor anthracycline antibiotics, aclacinomycin A and analogues. II: Structural determination. J. Antibiotics, 32, 801-819 (1979) 
    5. Hong, Y.-S., Hwang, C. K., Hong, S.-K., Kim, Y. H., and Lee, J. J., Molecular cloning and characterization of the aklavinone 11-hydroxyase gene of Streptomyces peucetius subsp. caesius ATCC 27952. J. Bacteriology, 22, 7096-7101 (1994) 
    6. Hwang, C. K., Kim, H.S., Hong, Y.-S., Kim, Y. H., Hong, S.-K., Kim, S.-J., and Lee, J. J., Expression of Streptomyces peucetius genes for doxorubicin resistance and aklavinone 11-hydroxylase in Streptomyces galilaeus ATCC 31133 and production of a hybrid aclacinomycin. Antimicrob. Agents Chemother., 39, 1616-1620 (1995) 
    7. Iguchi, H., Matsushita, Y., Ohmori, K., Hirano, S., Kiyosaki, T., Hori, S., Tone, H., and Oki, T., Studies on the absorption, excretion and distribution of aclacinomycin A: absorption, excretion and distribution of aclacinomycin A in mice, rabbits and dogs by photometric assay. Jpn. J. Antibiot., 33, 179-191 (1980b) 
    8. Kim, H. S., Kim, Y. H., Yoo, O. J., and Lee, J. J., Aclacinomycin X, a novel anthracycline antibiotic produced by Streptomyces galilaeus ATCC 31133. Biosci. Biotech. Biochem., 60, 906- 908 (1996a) 
    9. Kim, H. S., Hong, Y.-S., Kim, Y. H., Yoo, O. J., and Lee, J. J., New Anthracycline metabolites produced by the aklavinone 11-hydroxylase gene in Streptomyces galilaeus ATCC 31133. J. Antibiotics, 49, 355-360 (1996b) 
    10. Iguchi, H., Seryu, Y., Kiyosaki, T., Hori, S., Tone, H., and Oki, T., Studies on the absorption, excretion and distribution of aclacinomycin A: absorption, excretion and distribution of 14C- or 3H-aclacinomycin A in mice, rats and rabbits. Jpn. J. Antibiot., 33, 169-178 (1980a) 
    11. Yamaoka, K., Tanigawara, Y., Nakagawa, Y., and Uno, T., A pharmacokinetic analysis program (MULTI) for microcomputer. J. Pharmcobio. Dynamics, 4, 879-885 (1981) 
    12. Johdo, O., Watanabe, Y., Ishikura, T., Yoshimoto, A., Naganawa, H., Sawa, T., and Tacheuchi, T., Anthracycline metabolites from Streptomyces violaceus A262 II: New anthracycline epelmycins produced by a blocked mutant strain SU2-730. J. Antibiotics, 44, 1121- 1129 (1991) 
    13. Niemi, J., Ylihonko, K., Hakala, J., Parssinen, R., Kopio, A., and Mantsala, P., Hybrid anthracycline antibiotics: Producion of new anthracyclines by cloned genes from Streptomyces purpurascens in Streptomyces galilaeus. Microbiology, 140, 1351-1358 (1995) 
    14. Yoshimoto, A., Fujii, S., Johdo, O., Kubo, K., Ishikura, T., Naganawa, H., Sawa, T., Tacheuchi, T., and Umezawa, H., Intensely potent anthracycline antibiotic oxaunomycin produced by a blocked mutant of the daunorubicin-producing microorganism. J. Antibiotics, 39, 902-909 (1986) 

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