European Journal of Clinical Pharmacology

, Volume 45, Issue 2, pp 181–186

Decreased chloramphenicol clearance in malnourished Ethiopian children

  • M. Ashton
  • P. Bolme
  • E. Alemayehu
  • M. Eriksson
  • L. Paalzow


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.

Key words

Malnutrition Chloramphenicol children pharmacokinetics kwashiorkor marasmus 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ambrose PJ (1984) Clinical Pharmacokinetics of chloramphenicol and chloramphenicol succinate. Clin Pharmacokinet 9: 222–238Google Scholar
  2. Benet LZ, Galeazzi RL (1979) Noncompartmental determination of the steady-state volume of distribution. J Pharm Sci 15: 1071–1074Google Scholar
  3. Buchanan N, Van der Walt LA (1977) Chloramphenicol binding to normal and kwashiorkor sera. Am J Clin Nutr 30: 847–850Google Scholar
  4. Chatterjee KK, Mukherjee KL (1968) Phospholipids of the liver in children suffering from protein-calorie undernutrition. Br J Nutr 22: 145–151Google Scholar
  5. Doumas BT, Watson WA, Biggs HG (1971) Albumin standards and the measurement of serum albumin with bromocresol green. Clin Chim Acta 31: 87–96Google Scholar
  6. Editorial (1970) Classification of infantile malnutrition. Lancet II: 302–303Google Scholar
  7. Eriksson M, Paalzow L, Bolme P, Mariam TW (1983) Chloramphenicol pharmacokinetics in Ethiopian children of differing nutritional status. Eur J Clin Pharmacol 24: 819–823Google Scholar
  8. Glazko AJ (1966) Identification of chloramphenicol metabolites and some factors affecting metabolic disposition. Antimicrob Agents Chemother 6: 655–665Google Scholar
  9. Kauffman RE, Thirumoorthi MC, Buckley JA, Aravind MK, Dajani AS (1981) Relative bioavailability of intravenous chloramphenicol succinate and oral chloramphenicol palmitate in infants and children. J Pediatrics 99: 963–967Google Scholar
  10. Koup JR, Lau AH, Brodsky B, Slaughter RL (1979a) Chloramphenicol pharmacokinetics in hospitalized patients. Antimicrob Agents Chemother 15: 651–657Google Scholar
  11. Koup JR, Slattery JT, Gibaldi M (1979b) Single point clearance estimation. Res Comm Chem Pathol Pharmacol 25: 559–564Google Scholar
  12. Koup JR, Sack CM, Smith AL, Neely NN, Gibaldi M (1981) Rapid estimation of chloramphenicol clearance in infants and children. Clin Pharmacokinet 6: 83–88Google Scholar
  13. Krishnaswamy K (1978) Drug metabolism and pharmacokinetics in malnutrition. Clin Pharmacokinet 3: 216–240Google Scholar
  14. Krishnaswamy K (1987) Diseases of a Tropical Environment, in Drug Treatment: Principles and Practice of Clinical Pharmacology and Therapeutics, 3rd ed, Avery, G. (Ed.), Chapter 30. Livingstone, Edinburgh, pp. 1273–1315Google Scholar
  15. Mehta S, Nain CK, Kalsi HK, Mathur VS (1981) Bioavailability and pharmakokinetics of chloramphenicol palmitate in malnourished children. Ind J Med Res 74: 244–250Google Scholar
  16. Nahata MC, Powell DA (1983) Comparative bioavailability and pharmacokinetics of chloramphenicol after intravenous chloramphenicol succinate in premature infants and older patients. Dev Pharmacol Ther 6: 23–32Google Scholar
  17. Nahata MC (1987), Serum concentrations and adverse effects of chloramphenicol in pediatric patients. Chemotherapy 33: 322–327Google Scholar
  18. Sack CM, Koup JR, Opheim KE, Neeley N, Smith AL (1982) Chloramphenicol succinate kinetics in infants and young children. Ped Pharmacol 2: 93–103Google Scholar
  19. Sharma B, Metha S, Nain CK, Mathur VS (1986) Disposition of chloramphenicol in young rhesus monkeys with protein-energy malnutrition. Drug-Nutrient Interactions 4: 333–338Google Scholar
  20. Tandon BN, Ramanujan RA, Tandon HD, Gandhi PC (1974) Liver injury in proteincalorie malnutrition: an electron microscopic study. Am J Clin Nutr 27: 550–558Google Scholar
  21. Wargin WA, Wurster DE (1983) Determination of the rearrangement kinetics of chloramphenicol-3-monosuccinate using an automated HPLC system. Int J Pharmaceut 15: 37–48Google Scholar
  22. Wenk M, Vozeh S, Follath F (1984) Serum level monitoring of antibacterial drugs — a review. Clin Pharmacokinet 9: 475–492Google Scholar
  23. WHO Expert Committee (1988) The use of essential drugs — Model list of essential drugs (Fifth List). Technical Report Series 770, World Health Orginsation, GenevaGoogle Scholar
  24. Yamakawa T, Itoh S, Onishi S, Isobe K, Hosoe A, Nishimura Y (1984) Developmental changes in hepatic esterase activity towards chloramphenicol succinate and its Michaelis-Menten constant of liver, kidney and lung in human. Dev Pharmacol Ther 7: 205–212Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • M. Ashton
    • 1
  • P. Bolme
    • 2
  • E. Alemayehu
    • 3
  • M. Eriksson
    • 2
  • L. Paalzow
    • 1
  1. 1.Department of Biopharmaceutics and PharmacokineticsUppsala UniversityUppsalaSweden
  2. 2.Department of Pediatrics, Karolinska InstituteHuddinge Hospital and St Görans HospitalStockholmSweden
  3. 3.Department of Pediatrics and Child HealthEthio-Swedish Childrens' HospitalAddis AbebaEthiopia

Personalised recommendations