| Research Abstract |
It is very important to study the metabolism and action of antileukemic agents under the condition which precisely reflect the clinical pharmacokinetics. In this year, we studied cell growth inhibition of leukemic cell line (K562) by cytosine arabinoside (ara-C), using method of trypan blue dye exclusion assay (TB) and clonogenic assay (CA) under the drug concentration regulated by automatic simulation system which was established last year. Under the condition of clinically regular dose ara-C (100mg/m_2) and equal area under the curve (AUC) each other, the cell growth by 2,4,8,16 hour infusion was 73%, 53%, 39%, 45% using TB,and 76%, 72%, 34%, 15% using CA respectively, compared with control. More obvious time dependent inhibition by ara-C was observed using CA.We also compared the effect of daunorubicin (DNR) by simulation method with the data by conventional culture system. The cell growth was 82% of the control using CA under simulated condition with DNR 40mg/m_2 30min.infusion (Cmax ; 0.20 muM,t1/2beta ; 4.35 hr). On the other side, 0.022 muM was required to get the same growth inhibition effect by 24 hours incubation under condition of conventional culture system. About 9 times higher concentration was required in automatic simulation system compared with conventional culture system. This result was different from the the case with the ara-C in last year where the difference was about 80 times, suggesting the difference might depend on the action and metabolism of each drug. In addition, it was suggested that to estimate the anti-tumor effect of drug, automatic simulation system is superior than conventional culture system. And it was also suggested that CA was better method than TB to judge the cell growth inhibition effect. Now we are studying cell growth inhibition under condition to simulate ara-C and DNR simultaneously using automatic simulation system.
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