Gamelli R L, Foster R S, Whisnant J K
Transplantation. 1983 Jan;35(1):12-4. doi: 10.1097/00007890-198301000-00003.
By using an in vitro quantitative clonal culture technique for bone marrow granulocyte/macrophage progenitor cells (GM-CFC), we studied the effects of cimetidine alone and cimetidine plus azathioprine on bone marrow toxicity in C57BL/6 mice. Femoral bone marrow showed no effect of cimetidine in doses from 31.25 to 500 mg/kg on either marrow cellularity or the number of GM-CFC. Cimetidine pretreatment with single doses of 62.5 mg/kg or 250 mg/kg had no effect on the bone marrow suppression of azathioprine at 100 mg/kg. Chronic cimetidine pretreatment at 62.5 mg/kg daily for 7 days also had no effects on the single-dose azathioprine toxicity. Cimetidine given either before or after azathioprine had no effect on the rate or final level of recovery of GM-CFC in the marrow after depletion by azathioprine. Cimetidine in vitro at doses of 3.1 to 200 micrograms/ml caused no alteration in the proliferative response of the GM-CFC. Analysis of the serum colony-stimulating activity 1 to 24 hr following doses of cimetidine of either 12.5 mg/kg or 31 mg/kg caused no change in the serum colony-stimulating activity. We could find no evidence that at clinically relevant doses, cimetidine increased the hematopoietic toxicity of the azathioprine or altered the rate of bone marrow recovery after azathioprine depletion.
通过使用体外定量克隆培养技术检测骨髓粒细胞/巨噬细胞祖细胞（GM-CFC），我们研究了西咪替丁单独使用以及西咪替丁联合硫唑嘌呤对C57BL/6小鼠骨髓毒性的影响。股骨骨髓显示，剂量为31.25至500mg/kg的西咪替丁对骨髓细胞数量或GM-CFC数量均无影响。单剂量62.5mg/kg或250mg/kg的西咪替丁预处理对100mg/kg硫唑嘌呤的骨髓抑制作用没有影响。每天62.5mg/kg的西咪替丁连续预处理7天对单剂量硫唑嘌呤毒性也没有影响。在硫唑嘌呤之前或之后给予西咪替丁对硫唑嘌呤耗竭后骨髓中GM-CFC的恢复速率或最终水平没有影响。体外剂量为3.1至200μg/ml的西咪替丁对GM-CFC的增殖反应没有改变。分析12.5mg/kg或31mg/kg西咪替丁给药后1至24小时的血清集落刺激活性，发现血清集落刺激活性没有变化。我们没有发现证据表明在临床相关剂量下，西咪替丁会增加硫唑嘌呤的造血毒性或改变硫唑嘌呤耗竭后骨髓的恢复速率。
