YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Pharmacokinetic Study of CKD-602, A New Camptothecin Derivative: Distribution, Metabolism and Excretion

신규 캄토테신계 항암제 CKD-602의 약물동태: 분포, 대사 및 배설

  • Lee, Ju-Mong (Chong Kun Dang Research Center, Chong Kun Dang Corporation) ;
  • Lee, Jun-Hee (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
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Abstract

The distribution, metabolism and excretion of CKD-602{20(S)-7-[2-(N-Isopropylamino)ethyl]camptothecin HCI), a new camptothecin derivative, were investigated in rats after a sing le administration of CKD-602. 1. The tissue levels of CKD-602 given to mice by the intravenous route at a dose of 20mg/kg were the highest in intestine, followed in descending order by kidney, liver, stomach,lung, heart, spleen and plasma. The concentrations of CKD-602 after 24hrs decreased to less than 2% of the peak level in most tissues except the skin. The urinary and fecal excretion of CKD-602 were 47.6% and 44.4% of the administered dose, respectively, with 0.7% remaining in the rinse. 2. After administration of CKD-602 at 10mg/kg in rats, metabolism of this compound was examined in plasma, urine, and feces. The plasma samples were collected for 24hr, urinary and fecal samples for 72hr. While any peak of CKD-602 in HPLC chromatograms was not detected from plasma and urine it was detected in feces (peaks, 9.8 min). However, additional peak area was about 0.5% of the peak area of parent CKD-602. Therefore, CKD-602 may be eliminated with the parent form and rarely metabolized in the body. 4. After I.v. administration of CKD-602 at 10mg/kg in rats, urinary and fecal excretions were examined for 72hrs post dose period. 87% of total urinary excretion of CKD-602 was excreted within 8hr after administration, 53%, and 32% of total fecal excreted amounts were determined in 0-24 hr and 24-48hr periods, respectively. The total excretion amounts of CKD-602 into urine and feces were 94% of the administered dose.

Keywords

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