This document discusses the pharmacokinetics of the antibiotic chloramphenicol. It is well absorbed in the gastrointestinal tract and widely distributed throughout the body, including into the central nervous system. It is metabolized in the liver. Chloramphenicol is effective against both gram-positive and gram-negative bacteria but has more effect on gram-negatives. Its uses are now limited due to its toxicity, especially in newborn infants where it can cause a potentially fatal gray baby syndrome.

1. Dr.Zulcaif Ahmad

2. CONTENTS
• Pharmacokinetics
• Absorption
• Distribution
• Fate and excretion

3. INTRODUCTION
Although an effective broad-spectrum
antibiotics, its uses are limited by its
serious toxicity. Now is rarely used except
for severe infective diseases.
It is well absorbed and widely distributed,
including to the CNS. It is metabolized by
glucuroni-dation in the liver.

4. PHARMACOLOGIC EFFECTS
Chloramphenical is active against a broad range
of organisms,
including G+and G- bacteria (including
anaerobes).
But, its effects on G-bacteria is better than on
G+ bacteria, especially Salmonella typhi.

6. ABSORPTION
Absorbed from the GIT tract.
Peak con. Of 10 to 13ug/ml occurs with in 2 to 3 hr
after the administration of 1g dose .
The hydrolysis of cholremphenicol succinate is
due to the esterases enzyme present in kidney,
liver and lungs.
Poor renal function in the neonates and other
state of renal insufficiency result in increased
plasma conc. Of chloremphinicol succinate

10. CHLORAMPHENICOL
Mechanisms of action
Mechanisms of resistance
Clinical uses
Adverse effects

11. MECHANISMS OF ACTION
inhibits bacterial protein synthesis.
CAP binds 50S subunit and block elongation by inhibiting the formation of
initiation complexes and peptidyltransferase;
CAP is primarily bacteriostatic, but it may be bactericidal to some strains
of microorganisms even at lower concentration:

14. MECHANISMS OF RESISTANCE
reduced membrane permeability
mutation of the 50S ribosomal subunit
elaboration of chloramphenicol acetyltransferase

15. ADVERSE EFFECTS

16. . Toxicity for Newborn Infants (Gray-baby syndrome) Be seen in neonates,
especially premature infants, who have been given relatively large doses of
CAP.
The inadequate renal elimination mechanism of neonate and the inactive
metabolites also contributes to the occurrence of the syndrome.

17. . Gastrointestinal reaction. nausea, vomiting,diarrhea
. Hypersensitivity reactions
. A rare anemia, probably immunological in origin but often fatal

20. DRUG INTERACTION
Irreversibly inhibit the microsomal enzyme p-450.
Conversely other drug may alter the elimination of chloremphenicol