Haemotoxicity of chloramphenicol succinate in the CD-1 mouse and Wistar Hanover rat

1 Chloramphenicol has been widely used in the treatment of serious infectio ns including typhoid fever and meningitis. However, the drug is haemotoxic in man inducing firstly, a reversible, dose-dependent anaemia which develop s during treatment, secondly, an often fatal aplastic anaemia with pancytop enia and acellular marrow, and thirdly, leukaemia. 2 We investigated the haemotoxicity of chloramphenicol succinate (CAPS) in female CD-1 mice in repeat dose studies, to compare the response with the r eversible anaemia reported in man. Studies in male Wistar Hanover rats were also carried out. 3 CAPS was gavaged daily to mice at dose levels from 800-2000 mg/kg for sev en days. Values were significantly reduced for reticulocytes at 1700 and 20 00 mg/kg, and for erythrocytes (RBC), haematocrit (HCT), and haemoglobin (H b) at 2000 mg/kg. platelet and white blood cell (WBC) counts were unaffecte d. 4 Mice were dosed with CAPS at 1400 mg/kg for 10 days and sampled at 1, 4 a nd 15 days after the last dose. At day 1 post dosing, REC, BCT and Hb value s were significantly reduced, but returned to normal (or above normal) by d ay 4 or 15. 5 CAPS from 2000-4000 mg/kg was gavaged to rats daily for 19 days. Nb value s were significantly lower at 3600 and 4000 mg/kg; reticulocytes were not r educed. WBC and platelet counts, in general, were unaffected. 6 Levels of apoptosis in marrow mononuclear cells were increased in CAPS-tr eated mice, but not in CAPS-treated rats. Serum biochemistry parameters, in general, showed few changes of toxicological significance. 7 We conclude that the administration of CAPS to CD-1 mice induced haematol ogical changes showing close parallels with the chloramphenicol-induced rev ersible anaemia seen in man.