Firsov A A, Geodakian S V, Egorov L V, Terent'eva T G
Antibiot Med Biotekhnol. 1987 Oct;32(10):773-7.
Tissue pharmacokinetics of aclarubicin and its active metabolites was studied with high performance liquid chromatography. The drug was administered to rats intravenously in single doses of 5 and 10 mg/kg and orally in a single dose of 10 mg/kg. With both the administration routes the highest concentrations of the drug and its metabolites were attained in the lymph nodes. Then followed the spleen and lungs. The lowest content of the drug was detected in the heart. The total values of the areas under the concentration/time curves for aclarubicin and its metabolites in the tissues of the heart, lungs, lymph nodes and spleen after oral administration were respectively 2, 3, 4 and 7 times lower than those after the drug intravenous administration in the same dose. The concentrations of the active metabolites MA144N1 and MA144T1 exceeded those of aclarubicin and were detected in the tissues within a longer period as compared to the unchanged drug. With repeated administration preferential accumulation of the metabolites in the tissues and their increased contribution to the aclarubicin antitumor effect could be suspected.
采用高效液相色谱法研究了阿柔比星及其活性代谢产物的组织药代动力学。分别以5mg/kg和10mg/kg的单剂量静脉注射以及10mg/kg的单剂量口服给药于大鼠。两种给药途径下,药物及其代谢产物在淋巴结中的浓度最高,其次是脾脏和肺,心脏中的药物含量最低。口服给药后,心脏、肺、淋巴结和脾脏组织中阿柔比星及其代谢产物的浓度/时间曲线下面积总值分别比相同剂量静脉给药后低2、3、4和7倍。活性代谢产物MA144N1和MA144T1的浓度超过阿柔比星,且与未变化的药物相比,在组织中检测到的时间更长。反复给药时,可怀疑代谢产物在组织中优先蓄积,且它们对阿柔比星抗肿瘤作用的贡献增加。