Chloramphenicol pharmacokinetics in infants less than three months of age in the Philippines and The Gambia


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Abstract

Background.The broad antimicrobial spectrum and affordable price of chloramphenicol make it an attractive first line treatment option for children with severe illnesses in developing countries. Little is known, however, about its pharmacokinetics in young infants in these settings.Methods.We studied infants younger than 3 months of age hospitalized in Manila, Philippines and The Gambia with possible severe bacterial infections likely to benefit from treatment with chloramphenicol. Infants in the first week of life received intramuscular doses of 25 mg/kg chloramphenicol once daily, twice daily in the second through fourth week of life and three times daily from 5 to 12 weeks of age. Blood samples were taken at 0.5, 1, 2 and 3 h after the first dose, 1 h before the second dose and before the repetition doses on subsequent days. In the Philippines a second group of infants was treated with oral chloramphenicol according to the same dosage schedule.Results.Thirty-eight infants received intramuscular chloramphenicol, and 20 received oral drug. Intramuscular administration resulted in therapeutic concentrations (10 to 25 μg/ml) in 73 to 86% of children in each of the three age groups in the first 6 h and in 50 to 80% on Days 2 and 3. Between 33 and 38% of children had potentially toxic values on Days 2 and 3. In contrast, after oral administration, only about one-half of the children reached therapeutic values in serum at any time up to Day 3 after start of treatment.Conclusions.Intramuscular chloramphenicol can be used as a second line drug for the treatment of severe infections in infants younger than 90 days of age, where third generation cephalosporins are not available. It quickly achieves therapeutic values in a high proportion of children. However, severe infections should not be treated with oral chloramphenicol in this age group, because therapeutic serum concentrations were inconsistently achieved.

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