INDICES> Grey syndrome with very high chloramphenicol plasma levels (2)

[Beatriz Ortiz-Christiansen <Bchristnsn@aol.com>]

INDICES> Grey syndrome with very high chloramphenicol plasma levels (2)
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>We would like to know the mechanism by which high plasma level of
>chloramphenicol causes Grey syndrome, a potentially fatal condition.  
 
In the newborn there are a number of liver enzymes which are not fully able 
to metabolize certain drugs. In the case of chloramphenicol, the absence or 
deficiency of glucoronyl transferase activity in the newborn will delay the 
metabolism of the drug to the inactive form. The result will be an elevated 
chloramphenicol level which can cause cardiovascular collapse and death - 
Gray baby syndrome.

Beatriz Ortiz-Christiansen, BS Pharm., RPh., MHS
CORTSEN Consulting Group, Inc.
e-mail: bchristnsn@aol.com

PS: For more information I have copied below a citation and abstract from  
Medline:

TITLE: Chloramphenicol toxicity in neonates: its incidence and prevention. 
AUTHORS: Mulhall A; de Louvois J; Hurley R SOURCE: Br Med J (Clin Res Ed) 
1983 Nov 12;287(6403):1424-7 CITATION IDS: PMID: 6416440 UI: 84054121 
ABSTRACT: The incidence of dose related chloramphenicol toxicity was 
determined in 64 neonates from 12 hospitals. Ten of the 64 exhibited symptoms 
attributed clinically to chloramphenicol toxicity. Nine received the dose 
prescribed and one an overdose. Symptoms of the grey baby syndrome were 
observed in five of the 10 babies; four babies suffered reversible 
haematological reactions; and one baby was described as very grey. Peak serum 
chloramphenicol concentrations in these 10 babies ranged from 28 to 180 mg/l 
and trough concentrations from 19 to 47 mg/l. Serum chloramphenicol 
concentrations above the therapeutic range (15-25 mg/l) were observed in a 
further 27 neonates (two had received a 10-fold overdose), none of whom 
showed signs of toxicity. Serious toxicity was associated with either 
prescription of dosages greater than that recommended or overdosage of 
chloramphenicol. High concentrations in young neonates may be avoided by 
prescribing and giving the recommended dose and then careful monitoring; 
concentrations should be maintained between 15 and 25 mg/l. No babies with 
concentrations within this range showed clinical signs of toxicity. 

[thanks, Beatriz! WB]
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