Chloromycetin Pharmacology, Pharmacokinetics, Studies, Metabolism - Chloramphenicol

Chloromycetin Pharmacology, Pharmacokinetics, Studies, Metabolism - Chloramphenicol

CLINICAL PHARMACOLOGY

In vitro chloramphenicol exerts mainly a bacteriostatic effect on a wide range of gram-negative and gram-positive bacteria and is active in vitro against rickettsias, the lymphogranuloma-psittacosis group and Vibrio cholerae. It is particularly active against Salmonella typhi and Hemophilus influenzae. The mode of action is through interference or inhibition of protein synthesis in intact cells and in cell-free systems.

Chioramphenicol administered orally is absorbed rapidly from the intestinal tract. In controlled studies in adult volunteers using the recommended dosage of 50 mg/kg/day, a dosage of 1 g every 6 hours for 8 doses was given. Using the microbiological assay method, the average peak serum level was 11.2 mcg/mL one hour after the first dose. A cumulative effect gave a peak rise to 18.4 mcg/ mL after the fifth dose of 1 g. Mean serum levels ranged from 8 to 14 mcg/mL over the 48-hour period. Total urinary excretion of chloramphenicol in these studies ranged from a low of 68% to a high of 99% over a three-day period. From 8 to 12% of the antibiotic excreted is in the form of free chloramphenicol; the remainder consists of microbiologically inactive metabolites, principally the conjugate with glucuronic acid. Since the glucuronide is excreted rapidly, most chloramphenicol detected in the blood is in the microbiologically active free form. Despite the small proportion of unchanged drug excreted in the urine, the concentration of free chloramphenicol is relatively high, amounting to several hundred mcg/mL in patients receiving divided doses of 50 mg/kg/day. Small amounts of active drug are found in bile and feces. Chloramphenicol diffuses rapidly, but its distribution is not uniform. Highest concentrations are found in liver and kidney, and lowest concentrations are found in brain and cerebrospinal fluid. Chloramphenicol enters cerebrospinal fluid even in the absence of meningeal inflammation, appearing in concentrations about half of those found in blood.