Description
Chloramphenicol palmitate is an orally bioavailable ester prodrug form of the antibiotic chloramphenicol. It is hydrolyzed in the small intestine to release chloramphenicol. Formulations containing chloramphenicol palmitate were previously used in the treatment of severe bacterial infections.
Chemical Properties
white crystals
Originator
Chloromycetin,Parke Davis,US,1951
Uses
antibacterial, antirickettsial
Uses
Chloramphenicol Palmitate is a Chloramphenicol (C325030) derivative, a broad spectrum antibiotic obtained from cultures of the soil bacterium Streptomyces venezuelae. It has a broad spectrum of activity against Gram-positive and gram-negative bacteria. Antibacterial; antirickettsial.
Uses
Chloramphenicol palmitate is prepared by acylation of chloramphenicol with palmitic acid. Although chloramphenicol palmitate is a more hydrophobic drug which should enhance bioavailability, the primary advantage of the ester is to mask the taste of chloramphenicol in oral formulations. Chloramphenicol palmitate is significantly less active than chloramphenicol but acts as a prodrug, being readily hydrolysed by acid and esterase in the gut to release chloramphenicol.
Definition
ChEBI: Chloramphenicol palmitate is a hexadecanoate ester. It is functionally related to a chloramphenicol.
Application
Chloramphenicol palmitate was synthesized by Parke Davis Co. in 1952. It has a much less bitter taste than chloramphenicol and is suitable for oral administration, especially for children. The palmitate shows a higher serum level after oral administration than chloramphenicol does and acts the same as chloramphenicol in vivo.
Manufacturing Process
1,674 g of palmitoyl chloride is added to 1,870 g of D(-)-threo-1-pnitrophenyl-2-dichloroacetamidopropane-1,3-diol (chloramphenicol) in 2,700
cc of pyridine and the solution stirred for 1 hour. The mixture is poured into
16 liters of water and the solid collected. Recrystallization of the crude product
from benzene yields the desired D(+)-threo-1-p-nitrophenyl-
1dichloroacetamido-3-palmitoyloxypropane-1-ol in pure form: MP 90°C.
brand name
Chloromycetin Palmitate (Parke-
Davis).
Therapeutic Function
Antibacterial; Antirickettsial
General Description
Chloramphenicol palmitate is the palmitic acid ester ofchloramphenicol. It is a tasteless prodrug of chloramphenicolintended for pediatric use. The ester must hydrolyze invivo following oral absorption to provide the active form.Erratic serum levels were associated with early formulationsof the palmitate, but the manufacturer claims that thebioavailability of the current preparation is comparable tothat of chloramphenicol itself.
Safety Profile
Moderately toxic by
oral route. An experimental teratogen. Other
experimental reproductive effects. An
antibiotic. When heated to decomposition it
emits very toxic fumes of NOx and Cl-. See
also other chloramphenicol entries.
Purification Methods
The palmitate crystallises from *benzene or xylene with m 105-106o and [] D –39.5o (c 2, Et2O), max 267.3nm. [Edgerton et al. J Am Chem Soc 77 27 1955, Beilstein 13 IV 2753.]
References
[1] AMBROSE P J. Clinical pharmacokinetics of chloramphenicol and chloramphenicol succinate.[J]. Clinical Pharmacokinetics, 1984, 9 3: 222-238. DOI:
10.2165/00003088-198409030-00004
