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Chloramphenicol

First isolated from Streptomyces venezuelae

in 1947, this antibiotic has a very broad

spectrum including Gram +ve, Gram -ve and

a special use against typhoid.

This agent is now produced by total

synthesis.

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Mechanism of action

It inhibits protein biosynthesis in both Gram(+)

and Gram(-)bacteria.

It is a bacteriostatic agent.

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Metabolism

Metabolism is mainly through the formation of

the C3-glucuronide metabolite that is the soluble

excretable metabolite (Phase 2).

The reduction of the nitro compound to the

amine, dechlorination and the hydrolysis of the

amide bond may also occur (Phase 1).

All these metabolites are inactive.

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Pharmacokinetic Properties

It is well absorbed then well distributed to

tissues.

It shows about 60% protein binding.

It has a bitter taste, which can be masked by the

use of the palmitate ester at the 3-hydroxyl group

in pediatric oral suspensions.

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Structure Activity Relationship

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Structure Activity Relationship

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Replacement of the primary or secondary

alcohol by alkyl group decreases activity.

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Extending the length or branching of the side

chain leads to loss of activity.

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Toxicity

It can cause a dose-related bone marrow

depression and may precipitate leukemia.

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Toxicity

A very small percent of patients (one in every

25,000 to 40,000 cases of therapy) may develop

aplastic anemia and results from loss of both

white and red cells precursors.

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Heme :

C34H32O4N4FeOH

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Resistance

Enzymes that cause acetylation of the hydroxyl

groups (especially the secondary alcohol),

resulting in a decreased ability of binding to

the ribosomes.

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Acetylation of the secondary Alcohol

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