The sensitivity of human bone marrow granulocyte/monocyte precursor cells to phenylbutazone,oxyphenbutazone and gamma-hydroxyphenylbutazone in vitro, with observations on the bone marrow colony formation in phenylbutazone-induced granulocytopoenia

The inhibitory actions of phenylbutazone, oxyphenbutazone and γ-hydroxyphenylbutazone on the growth of human bone marrow granulocyte/monocyte colonies in vitro have been compared. Oxyphenbutazone is more toxic than phenylbutazone in this system, γ-hydroxyphenylbutazone is inhibitory over a wider concentration-range than either phenylbutazone or oxyphenbutazone, but has about the same inhibitory potency as phenylbutazone at concentrations corresponding to the peak plasma concentrations during treatment. Three patients who had recovered from phenylbutazone-induced bone marrow depression with neutropoenia were studied. The proliferative capacity of the bone marrow from all three patients was reduced as judged by the measured formation of granulocyte/monocyte colonies in vitro. The sensitivity of the patients' bone marrow to inhibition by either phenylbutazone (two patients) or by oxyphenbutazone (three patients) was compared with that of normal subjects' bone marrow. Increased sensitivity to phenylbutazone was demonstrated in the patients. The difference between the patients' and normal subjects' marrow with respect to their sensitivity to oxyphenbutazone was insignificant. The present results are compared with the results of similar studies with other drugs which produce neutropoenia. It is concluded that they are not inconsistent with the suggestion that phenylbutazone-induced neutropoenia is due to an underlying marrow abnormality.