Delayed clearance of chloramphenicol from serum in patients with hematologic toxicity.

By LEIF G. SUHRLAND AND AUSTIN S. WEISBERGER T HE UNCOMMON OCCURRENCE of aplastic anemia following the therapeutic administration of chloramphenicol is well documented.’ However, erythropoietic depression associated with changes in iron metabolism, reticulocytopenia and vacuolization of erythroblasts is more frequent.2’3 If chloramphenicol is continued after these changes appear, leukopenia and thrombocytopenia may subsequently develop. The relationship of this type of toxicity to aplastic anemia has not been established, but it would seem essential to consider erythropoietic toxicity potentially dangerous and an indication to discontinue the drug. Therefore, it would be important to identify those individuals who are most susceptible to hematologic toxicity on therapeutic doses of chloramphenicol before a treatment program is undertaken. The erythropoietic depression occurring in patients receiving chloramphenicol is dose-related, and elevated blood levels of free chloramphenicol have been demonstrated in all patients developing erythropoietic depression.4’5 The blood level of free chioramphenicol is dependent in part upon the rate of conversion to the glucuronide form by the liver and in part on the limited ability of the kidney to excrete free chloramphenicol. Therefore, in liver or renal disease in which detoxification or elimination of free chioramphenicol is impaired, higher levels of the free form are often found and are associated with an increased incidence of erythropoietic depression.6 However, not all patients with liver or renal disease manifest an elevation of free chloramphenicol in the serum and these patients do not develop hematologic toxicity with ordinary therapeutic doses of chloramphenicol. It may be postulated then, that those patients who develop erythropoietic depression may clear the blood of free chloramphenicol at a slower rate than those who do not develop hematologic toxicity. The present study was undertaken to determine if patients who develop toxicity do indeed have an altered excretion pattern. In this study, the plasma clearance of a test dose of chloramphenicol was determined in patients who had previously manifested erythropoietic toxicity associated with high serum free chloramphenicol levels. As was expected, a significant impairment of chloramphenicol clearance was demonstrable in these individuals when compared to clearances in patients who had not developed erythropoietic toxicity.