Home › Pharmacology › Chloramphenicol

Chloramphenicol

Chloramphenicolum

For medical students2 min readUpdated 2026-10-10

Chloramphenicol (Chloramphenicolum) is a broad-spectrum bacteriostatic antibiotic. It inhibits protein synthesis in microbial cells but requires strict indications due to high toxicity and significant effects on the metabolism of other drugs.

FormulationsTablets, capsules, eye drops (0.25%)

TargetBacterial 50S ribosomal subunit

MechanismBacteriostatic

MetabolismGlucuronidation and microsomal reduction

Mechanism of Action and Effects

Chloramphenicol (Chloramphenicolum) is a classic broad-spectrum antibiotic. Its primary site of action is the 50S ribosomal subunit of the bacterial cell. By binding to it, the drug disrupts protein synthesis at the translation stage. In terms of its mechanism, it is a bacteriostatic antibiotic: it does not kill microorganisms directly, but halts their growth and reproduction, allowing the immune system to clear the infection independently.

Pharmacokinetics and Metabolism

Biotransformation of the drug occurs in the liver and involves two major pathways. The first is reduction of the nitro group via microsomal enzymes. The second involves biosynthetic conjugation reactions, specifically glucuronidation (binding with endogenous glucuronic acid).

A critical pharmacokinetic feature of chloramphenicol is enterohepatic circulation (circulatio enterohepatica). The drug is excreted by the liver (hepar) into the bile as inactive glucuronides. Upon reaching the intestinal lumen (lumen intestini), these conjugates undergo hydrolysis (cleavage of the bond). This releases the active lipophilic substance, which is readily reabsorbed through the intestinal wall into the portal vein system (vena portae) and returned to the liver. This cyclic process prolongs the antibiotic's action and results in a significant delay in the ultimate elimination of a portion of the dose via the intestine.

Drug Interactions

The drug requires extreme caution during combination therapy due to two types of interactions:

Pharmacokinetic interaction: Chloramphenicol inhibits hepatic microsomal enzyme activity. This slows down the metabolism of drugs cleared by the liver (e.g., the oral anticoagulant warfarin or the antiepileptic drug phenytoin). Their half-life ($t_{1/2}$) increases, sharply raising the risk of toxicity.
Pharmacodynamic antagonism: Being a bacteriostatic agent, chloramphenicol weakens the effect of bactericidal antibiotics (penicillins, aminoglycosides) whose targets are actively dividing cells.

Side Effects and Contraindications

Hemolytic anemia: In patients with a genetic erythrocyte glucose-6-phosphate dehydrogenase deficiency (a pathology frequently found in tropical and subtropical regions), drug metabolism proceeds with quinone formation. This triggers acute erythrocyte hemolysis.
Pediatrics: The drug is strictly contraindicated in neonates during the first weeks of life. In the embryonic period and in infants, hepatic enzyme systems (especially conjugation processes involving glucuronyl transferase) are immature. This leads to fatal accumulation of toxic metabolites.
Lactation: Chloramphenicol passes into breast milk, reaching concentrations of about 50% of plasma levels. Even microdoses can cause allergic or toxic reactions in the infant, making maternal use an absolute contraindication to breastfeeding.

Formulations

The drug is available in the following formulations:

Tablets 0.25 g and 0.5 g;
Extended-release tablets 0.65 g;
Capsules 0.1 g, 0.25 g, and 0.5 g;
Eye drops (0.25% solution in 10 ml vials).

Administered orally at a dose of 0.25–0.5 g.

Mnemonic

Chloramphenicol binds to the 50S subunit: the Roman numeral L represents 50, corresponding to the first letter of its Latin synonym Laevomycetinum.

Frequently asked questions

What hematologic side effects are caused by chloramphenicol?

Chloramphenicol causes bone marrow suppression, including reversible and irreversible damage. Major hematologic side effects include:

Hemolytic anemia — develops in glucose-6-phosphate dehydrogenase deficiency due to quinone formation and subsequent hemolysis.
Reversible erythropoiesis suppression — a dose-dependent complication.
Aplastic anemia — a rare, potentially fatal idiosyncratic complication characterized by pancytopenia (suppression of erythroid, myeloid, and megakaryocytic lineages).

What specific toxic syndrome develops in newborns receiving chloramphenicol?

Neonates receiving chloramphenicol may develop "grey baby syndrome." This specific toxic complication arises when high doses of the drug are administered. The pathogenesis relates to the immaturity of hepatic metabolic enzyme systems in the first weeks of life, particularly glucuronyl transferase deficiency. This impairs detoxification, causing toxic drug metabolites to accumulate in the infant's body.

The metabolism of which drugs is slowed when co-administered with chloramphenicol?

Co-administration with chloramphenicol slows the metabolism of drugs cleared by the liver, including:

Phenytoin.
Warfarin.

This metabolic deceleration occurs because chloramphenicol inhibits hepatic microsomal enzyme activity, leading to an increased half-life of these drugs and a heightened risk of toxicity.

Which microorganisms are susceptible to chloramphenicol (antimicrobial spectrum)?

Chloramphenicol is a broad-spectrum antibiotic active against:

Gram-positive bacteria.
Gram-negative bacteria.
Intracellular parasites.

In clinical practice, it is specifically used to treat infections caused by Yersinia pathogens and typhoid fever (Salmonella typhi).

With which antibiotic classes does chloramphenicol show pharmacodynamic antagonism?

Chloramphenicol exhibits pharmacodynamic antagonism with bactericidal antibiotics that act on dividing cells, such as:

Penicillins
Aminoglycosides

This interaction occurs because chloramphenicol, as a bacteriostatic agent, halts bacterial growth and division, thereby weakening the therapeutic efficacy of bactericidal drugs that target actively multiplying microorganisms.

Why should chloramphenicol not be combined with penicillins?

Chloramphenicol is a bacteriostatic agent that halts cell division. Penicillins are bactericidal drugs active only against actively dividing bacteria. This results in pharmacodynamic antagonism.

What causes the high toxicity of the drug in newborns?

In infants during the first weeks of life, hepatic enzyme activity—specifically glucuronyl transferase—is reduced. This impairs conjugation reactions, causing toxic metabolites to accumulate in the body.

How does enterohepatic circulation affect chloramphenicol pharmacokinetics?

The drug is excreted in the bile as glucuronides, which are hydrolyzed in the intestine back into the active substance and reabsorbed into the bloodstream. This prolongs the antibiotic's duration of action.

What hematologic complication does chloramphenicol trigger in individuals from tropical regions?

In individuals with hereditary erythrocyte glucose-6-phosphate dehydrogenase deficiency, the drug is metabolized to quinone, which provokes hemolysis and the development of hemolytic anemia.

Go deeper

Ribosomal Protein Synthesis: Translation and Antibiotic Targets
Hepatic Microsomal Enzymes: Inducers and Inhibitors
Conjugation Reactions (Phase II Drug Biotransformation)
Pharmacogenetics: Enzyme Deficiencies and Atypical Drug Reactions
Perinatal Pharmacology: Excretion of Drugs in Breast Milk