Lack of predictability of chloramphenicol toxicity in paediatric patients.
We studied 45 patients (new-born to 12 year olds) who received 50-100 mg/kg/day chloramphenicol sodium succinate i.v. over 2-49 days for the treatment of central nervous system infections. Multiple blood samples were obtained to measure serum concentrations of chloramphenicol and its succinate ester by high pressure liquid chromatography (HPLC). Haematological parameters (haemoglobin, white cell, neutrophil, eosinophil and platelet counts) were also determined. Chloramphenicol therapy was effective in all patients. Anaemia was present in 10, leukopenia in four, neutropenia in four, and eosinophilia in 16 patients. These adverse effects occurred between 3 and 34 days after the initiation of therapy. Chloramphenicol therapy had to be discontinued only in three patients, who had absolute neutrophil counts less than 800/mm3. All adverse effects were reversible. Demographic factors, daily dose, duration of therapy, steady-state peak and trough serum concentrations, area under the serum concentration-time curve normalized for dose, and the elimination half-life were not correlated with the occurrence of adverse effects of chloramphenicol. The mean cumulative dose of chloramphenicol succinate was the only factor always higher but not statistically different in patients with adverse effects compared to those without. The mean cumulative dose of chloramphenicol succinate ranged from 1.2 to 1.8 g/kg in patients with adverse effects and 0.9-1.1 g/kg in those without. These data suggest that the adverse effects of chloramphenicol may not be predictable in paediatric patients. However, a high cumulative dose may possibly be an important factor in predisposing some patients to certain chloramphenicol toxicity.
Nahata
M C
MC
College of Pharmacy, Ohio State University, Columbus.
D000740:Anemia / Q000097:blood / Q000139:chemically induced; D002648:Child; D002675:Child, Preschool; D002701:Chloramphenicol / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D004802:Eosinophilia / Q000097:blood / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced / Q000503:physiopathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007970:Leukopenia / Q000097:blood / Q000139:chemically induced
D002701:Chloramphenicol