YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Pharmacokinetic Study of CKD-602, A New Camptothecin Derivative: Absorption

신규 캄토테신계 항암제 CKD-602의 약물동태: 흡수

  • Lee, Ju-Mong (Chong Kun Dang Research Center, Chong Kun Dang Corporation) ;
  • Sohn, Yong-Sung (Chong Kun Dang Research Center, Chong Kun Dang Corporation) ;
  • Kim, Joon-Kyum (Chong Kun Dang Research Center, Chong Kun Dang Corporation) ;
  • Shin, Hee-Jong (Chong Kun Dang Research Center, Chong Kun Dang Corporation) ;
  • Lee, Hyung-Ki (Chong Kun Dang Research Center, Chong Kun Dang Corporation) ;
  • Lee, Sang-Joon (Chong Kun Dang Research Center, Chong Kun Dang Corporation) ;
  • Hong, Chung Il (Chong Kun Dang Research Center, Chong Kun Dang Corporation)
  • Published : 1998.08.01
Download PDF
⟨ Previous Next ⟩

Abstract

The pharmacokinetics of CKD-602, a new camptothecin anticancer derivative, were studied in mice, rats and dogs following a single or multiple intravenous administration, and the following results were obtained. The blood levels of CKD-602 declined in biphasic fashions with peak plasma levels $(C_0)$ of $2.63{\mu}g/ml$ in mice, $2.27{\mu}g/ml$ in tumor bearing mice, $2.84{\mu}g/ml$ in rats at a dose of 20mg/kg, and of 0.02mcg/ml in dogs at a dose of 0.5mg/kg. The plasma half-lives $(t_{1/2}{\beta})$ were 9.55hr in mice, 9.94hr in tumor bearing mice, 9.98hr in rats and 12.75hr in dogs. AUC of CKD-602 was increased linearly with the dose at a range from 5 to 20mg/kg. Moreover, Cltot and Vdss were also not significantly changed with increasing the dose. On the other hand, after 5 daily intravenous bolus injection of CKD-602 (5mg/kg) in rats, $t_{1/2}{\beta}$, AUC and MRT of CKD-602 were 11.90hr, $3.19{\mu}g{\cdot}hr/ml$, and 11.61hr, respectively, which were slightly higher than after the single bolus injection.

Keywords

References

  1. J. Am. Chem. Soc. v.83 Plant antitumor agents: 1. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibition from camptotheca acuminata Wall, M. E.;Wani, M. C.;Cook, C. E.;Palmer, K. H.;Mcphail, A. T.;Sim, G. A.
  2. Cancer Chemother. Rep. v.56 Plasma camptothecin (NSC-100880) levels during a 5-day course of treatment: relation to dose and toxicity Creaven, P. J.;Allen, L. M.;Muggia, F. M.
  3. Cancer Chemother. Rep. v.56 Treatment of malignant melanoma with camptothecin (NSC-100880) in the treatment of advanced gastrointestinal cancer Moertel, C. G.;Scutt, A. J.;Reitemeier, R. J.;Hahn, R. G.
  4. Cancer Chemother. Rep. v.56 Phase I clinical trial of weekly and daily treatment with camptochecin (NSC-10080): correlation with preclinical studies Muggia, F. M.;Creaven, P. J.;Hansen, H. H.;Cohen, M. H.;Selawry, O. S.
  5. Biotechnology v.6 Topoisomerases as novel targets for cancer chemotherapy Bodley, A. L.;Liu, L. F.
  6. Science v.246 DNA topoisomerase I-targeted chemotherapy of human colon cancer in xenografts Giovanelta, B. C.;Stehlin, J. S.;Wall, M. E.;Wani, M. C.;Nicholas, A. W.;Liu, L. F.;Silber, R.;Potmesil, M.
  7. Tetrahedron: Asymmetry v.6 Enantioselective synthesis of 20(S)-camptothecin using sharpless catalytic asymmetric dihydroxylation Jew, S. S.;Ok, K. D.;Kim, H. J.;Kim, M. G.;Kim, J. M.;Kim, J. K.;Cha, K. H.;Lee, K. K.;Han, H. J.;Lee, H. S.
  8. Bioorg. Med. Chem. Lett. v.6 Synthesis and antitumor activity of 7-substituted 20-(RS)-camptothecin analogues Jew, S. S.;Kim, H. J.;Kim, M. G.;Roh, E. Y.;Cho, Y. S.;Kim, J. K.;Cha, K. H.;Lee, K. K.;Han, H. J.;Choi, J. Y.;Lee, H. S.
  9. Bioorg. Med. Chem. Lett. v.6 Synthesis and in vitro cytotoxicity of (RS)-20-dese-thyl-20-substituted campto thecin analouges Jew, S. S.;Kim, H. J.;Kim, M. G.;Roh, E. Y.;Cho, Y. S.;Kim, J. K.;Cha, K. H.;Lee, K. K.;Han, H. J.;Choi, J. Y.;Lee, H. S.
  10. Cancer Chemother. Rep. v.56 Treatment of malignant melanoma with camptothecin (NSC-100880) Gottlieb, J. Q. A.;Luce, J. K.
  11. Proc. Am. Assoc. Cancer Res. v.39 Antitumor activity of CKD-602, a novel camptothecin derivative Lee, J. H.;Sohn, Y. S.;Lee, J. M.;Kim, J. K.;Ahn, S. K.;Jew, S. S.;Park, J. G.;Hong, C. I.
  12. J. Pharm. Biomed. Anal. v.8 High performance liquid chromatographic analysis of the new antitumor drug SK&F104864-A (NSC609699) in plasma Beijnen, J. H.;Smith, B. R.;Keijer, W. J.;Van-Gijn, R.;Huinink, W. W.;Ten Bokkel;Vlasveld, L. Th.;Rodenhuis, S.;Underberg, W. J. M.
  13. J. Pharmacobio-Dyn. v.8 A pharma cokinetic analysis program (multi) for microcomputer Yamaoka, K.;Tanigawara, Y.;Nakagawa, T.;Uno, T.