DECREASED CHLORAMPHENICOL CLEARANCE IN MALNOURISHED ETHIOPIAN CHILDREN

The disposition of chloramphenicol and chloramphenicol monosuccinate has been studied in thirty-four Ethiopian children of varying nutritional status. After a single intravenous dose corresponding to chloramphenicol 25 mg per kg bodyweight, the plasma clearance of chloramphenicol monosuccinate was decreased only in severely malnourished children with kwashiorkor. Seventeen % of the dose (range 0-51 %) was recovered in urine as intact prodrug, indicating incomplete and variable bioavailability of chloramphenicol. Compared to underweight children, on average marasmic and kwashiorkor subjects exhibited a 2- and 3-fold increase, respectively, in the AUC of chloramphenicol. Elevated AUCs could be traced to reduced hepatic clearance of the drug. The unbound fraction both of chloramphenicol and its prodrug were slightly elevated in serum from kwashiorkor subjects. The possibility of using a single point measurement of plasma chloramphenicol as a guide to individualized dosage are discussed.