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 d...

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Bibliographic Details
Published in:European journal of clinical pharmacology 1993-09, Vol.45 (2), p.181-186
Main Authors: ASHTON, M, BOLME, P, ALEMAYEHU, E, ERIKSSON, M, PAALZOW, L
Format: Article
Language:English
Subjects:
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biological and medical sciences
Biological Availability
Child
Child, Preschool
Chloramphenicol - analogs & derivatives
Chloramphenicol - pharmacokinetics
Ethiopia
Female
Humans
Infant
Kwashiorkor - metabolism
Male
Medical sciences
Metabolic Clearance Rate
Nutrition Disorders - metabolism
Pharmacology. Drug treatments
Prodrugs - metabolism
Prodrugs - pharmacokinetics
Protein Binding
Protein-Energy Malnutrition - metabolism
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Summary: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.
ISSN:0031-6970
1432-1041
DOI:10.1007/BF00315503