Chloramphenicol hemisuccinate

Absorption

Chloramphenicol succinate has a high degree of interpatient variability, with a Tmax of 18 minutes to 3 hours. A 1g oral chloramphenicol succinate dose every 6-8 hours reaches a mean Cmax of 11.2μg/mL with a Tmax of 1 hour.

Toxicity

Patients experiencing an overdose may present with shock, cyanosis, and coma. Treat patients with symptomatic and supportive measures which may include administration of fluids, exchange transfusions, and administration of dopamine.

Description

Chloramphenicol succinate is a water-soluble prodrug form of the antibiotic chloramphenicol. It is a substrate for succinate dehydrogenase (SDH) and is oxidized by human liver and rat liver and kidney mitochondria to release chloramphenicol in vitro. Chloramphenicol succinate reduces human leukocyte migration in vitro. In vivo, chloramphenicol succinate reduces E. coli growth in rabbit and rat models of pyelonephritis when administered at doses of 150 and 200 mg/kg, respectively. Chloramphenicol succinate (20 mg/kg) reduces infarct size in a porcine model of myocardial ischemia-reperfusion injury. Formulations containing chloramphenicol succinate have been used in the treatment of severe bacterial infections.

The Uses of Chloramphenicol hemisuccinate

Chloramphenicol succinate is prepared by acylation of chloramphenicol with succinic anhydride to provide a water soluble pro-drug. Chloramphenicol succinate represents an alternative pro-drug strategy for chloramphenicol that has found a niche in surface antibiotic treatment in surgery. Chloramphenicol succinate is significantly less active than chloramphenicol but acts as a prodrug, forming chloramphenicol in the presence of succinate dehydrogenase.

Background

Chloramphenicol succinate is an ester prodrug of chloramphenicol. Chloramphenicol is a bacteriostatic antibiotic. Use of chloramphenicol succinate and chloramphenicol has decreased due to the risk of potentially fatal blood dyscrasias.
Chloramphenicol succinate was granted FDA approval on 20 February 1959.

What are the applications of Application

Chloramphenicol succinate is a prodrug of chloramphenicol

Indications

Chloramphenicol succinate is indicated to treat serious and susceptible bacterial infections where less dangerous drugs are ineffective or contraindicated.

Definition

ChEBI: Chloramphenicol succinate is a member of amphetamines and a hemisuccinate.

Pharmacokinetics

Chloramphenicol succinate is a prodrug of chloramphenicol, which binds to bacterial ribosomes and prevents translation. It has a narrow therapeutic index and a moderate duration of action. Patients should be counselled regarding the risk of serious fatal blood dyscrasias.

Metabolism

Chloramphenicol succinate is hydrolyzed to chloramphenicol. The propane-diol moiety of chloramphenicol can be metabolised through a number of pathways including glucuronidation, sulfate conjugation, phosphorylation, acetylation, and oxidation. The dichloroacetate moiety can be metabolised through hydrolysis of the amide group and dechlorination. The nitro functional group can also be metabolised to an aryl amine and aryl amide metabolite.