Hematopoietic toxicity by cimetidine. Reexamination using the antimetabolite azathioprine

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.