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

Abstract

1 Chloramphenicol has been widely used in the treatment of serious infections including typhoid fever and meningitis. However, the drug is haemotoxic in man inducing firstly, a reversible, dose-dependent anaemia which develops during treatment, secondly, an often fatal aplastic anaemia with pancytopenia 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 reversible 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 seven days. Values were significantly reduced for reticulocytes at 1700 and 2000 mg/ kg, and for erythrocytes (RBC), haematocrit (HCT), and haemoglobin (Hb) at 2000 mg/kg. Platelet and white blood cell (WBC) counts were unaffected. 4 Mice were dosed with CAPS at 1400 mg/kg for 10 days and sampled at 1, 4 and 15 days after the last dose. At day 1 post dosing, RBC, HCT and Hb values were significantly reduced, but returned to normal (or above normal) by day 4 or 15. 5 CAPS from 2000–4000 mg/kg was gavaged to rats daily for 19 days. Hb values were significantly lower at 3600 and 4000 mg/kg; reticulocytes were not reduced. WBC and platelet counts, in general, were unaffected. 6 Levels of apoptosis in marrow mononuclear cells were increased in CAPS-treated 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 haematological changes showing close parallels with the chloramphenicol-induced reversible anaemia seen in man.