Detailed investigation of bone marrow toxicity induced by anticancer drugs in various animals ③ :Examination for neutrophil kinetics in rats and comparative assessment of the species differences

Abstract

Background: Chemotherapy induced neutropenia and febrile neutropenia is one of frequent side effects in anticancer drug treatment and could be a cause to reduce relative dose intensity and therapeutic effects of the drugs. TK / TD simulation of bone marrow toxicity provide important information to minimize the risk of ineffectiveness and to increase the chances of prescribing a pharmacologically effective dose to patients / subjects. MTT (Mean transit time: the time required for metamyelocytes in bone marrow to mature and migrate to the peripheral blood) in rats was calculated to establish a TK / TD model reflected the dynamics of neutrophils in vivo. Based on the calculated MTT, species differences in bone marrow toxicity observed in previous studies will be discussed.

Methods: BrdU was dosed intraperitoneally once to rats. Peripheral blood was collected over time, and the ratio of BrdU⁺ cells in CD11b/c⁺RP-1⁺ cells was measured by FACS Celesta to calculate MTT.

Results: The percentage of BrdU⁺ cells in CD11b/c⁺RP-1⁺ cells showed a maximum value of 30-50% at 72-96 hours after administration. From these results, the MTT in rats was calculated to be about 64 hours. In the future, we will utilize the MTT calculated in the TK/TD model to improve the prediction accuracy of bone marrow toxicity in humans. At this meeting, the results of comparison of MTT in rats with those of other animal species will be presented.