chloramphenicol-succinate and chloramphenicol-palmitate

The effect of exocrine pancreatic function on the pharmacokinetics of the choramphenicol oral capsule (CAP-base), chloramphenicol palmitate oral liquid (CAP-P), and chloramphenicol succinate intravenous (CAP-S) formulations was evaluated in 10 patients, aged 16-30 yr, with cystic fibrosis. Pancreatic insufficiency was assessed in each patient by measuring the absorption of p-amino-benzoic acid after oral administration of N-benzoyl-L-tyrosyl-p-aminobenzoic acid which requires chymotrypsin to cleave p-aminobenzoic from the parent molecule. In a controlled cross-over design, the overall biodisposition of each formulation was assessed in each patient with or without concurrent administration of oral pancreatic enzymes. The relative amounts of active chloramphenicol available in systemic circulation was CAP-base greater than CAP-S greater than CAP-P. Pancreatic enzyme replacement had little effect on the biodisposition parameters for the CAP-base and CAP-S formulation, but significantly increased the peak concentration and bioavailability of the CAP-P formulation. Although pancreatic enzyme replacement improved the absorption characteristics of the CAP-P formulation, absorption remained prolonged and unreliable. Serum concentration-time profiles for either CAP-base or CAP-S consistently exceeded the MIC of important nonpseudomonal pathogens. This finding was not observed after CAP-P administration independent of pancreatic enzyme replacement. The results of this study support the continued clinical use of either CAP-base or CAP-S, but the cautious use of CAP-P formulations in CF patients with concurrent pancreatic insufficiency.

Topics: Administration, Oral; Adolescent; Adult; Chloramphenicol; Cystic Fibrosis; Humans; Injections, Intravenous; Pancreas; Pancreatic Function Tests; Pancreatin; Prodrugs; Time Factors

The comparative bioavailability of chloramphenicol from intravenous succinate, oral palmitate, and oral base preparations was studied in a crossover manner in 12 adult patients. Chloramphenicol was administered at a dose of 1 Gm every 6 hours, and blood samples were collected at steady state. For the succinate study, total urine output was also collected. The bioavailability of active chloramphenicol from the succinate preparation averaged 85.8 +/- 42.3 and 78.8 +/- 50.1 per cent of the free base and palmitate forms, respectively. This lower availability appeared to be due to variable excretion of unchanged succinate in the urine, averaging 27 +/- 11 per cent of the dose. Regardless of dosage form or route of administration, plasma chloramphenicol concentrations remained in the therapeutic range (5 to 25 mg/liter) for the entire dosage interval, implying that no change needs to be made when changing dosage form or route of administration. The interpatient variability, however, supports the need for monitoring of plasma chloramphenicol concentrations, especially in newborn infants, persons with liver disease, or those receiving other medications that alter chloramphenicol metabolism.

Topics: Administration, Oral; Adolescent; Adult; Aged; Biological Availability; Chloramphenicol; Chromatography, Gas; Drug Administration Schedule; Female; Humans; Injections, Intravenous; Male; Middle Aged

The absorption and disposition of orally administered chloramphenicol palmitate (chloramphenicol-P) was studied in seven neonates (four preterm, three term). The highest measured chloramphenicol serum concentrations occurred greater than or equal to 4 hours after the dose, and ranged from 5.5 to 23 micrograms/ml after doses of chloramphenicol-P 50 mg/kg/day orally. The dosage had to be increased in all preterm neonates from 25 mg/kg/day to 50 mg/kg/day to obtain adequate serum levels during therapy. In four neonates the apparent half-life could not be estimated, because there was no decline in serum concentrations. The apparent half-life was 3 and 6 hours, respectively, in two neonates in whom the serum concentration declined during the dosing interval. Urinary excretion of chloramphenicol and the glucoronide ester in three neonates varied from 24% to 55% of the total dose administered. These preliminary data suggest considerable variability in serum chloramphenicol levels when chloramphenicol-P is administered orally in neonates. The delay in achieving the maximum serum concentration, nondeclining serum curve, and low renal recovery is indicative of incomplete, prolonged, and erratic absorption, possibly related to delayed gastric emptying or decreased intraluminal hydrolysis of the palmitate ester.

Topics: Administration, Oral; Adsorption; Biological Availability; Chloramphenicol; Half-Life; Humans; Infant, Newborn; Infusions, Parenteral; Meningitis

When aromatic nitro compounds are reduced with zinc and calcium chloride and reacted with trisodium pentacyanoaminoferrate they give a purple product having an absorbance maximum between 480 and 540 nm. Applying this reaction, a quantitative method has been developed for the determination of chloramphenicol and its esters. Various reaction conditions have been standardized. Beer's law is obeyed in the concentration range of 4 to 32 micrograms/mL reaction mixture. Average recoveries and standard deviations were 99.78 +/- 0.627 and 99.90 +/- 0.660; 101.06 +/- 0.702; and 99.90 +/- 0.880% for chloramphenicol, chloramphenicol sodium succinate, and chloramphenicol palmitate, respectively. The method has also been applied to determine chloramphenicol and its esters as well as chloramphenical in the presence of combination drugs in dosage forms. The presence of benzocaine, lignocaine, sulfadiazine, nitrofurantoin, ascorbic acid, hydrocortisone, prednisolone, streptomycin, and tetracycline does not interfere with the proposed spectrophotometric procedure. The method does not require prior separation of chloramphenicol from combination drugs.

Topics: Capsules; Chloramphenicol; Drug Combinations; Injections; Ointments; Solutions; Spectrophotometry, Ultraviolet; Suspensions