Chloramphenicol succinate

Incompatibilities Do not mix IV minocycline before or during administration with any solutions containing the following Adrenocorticotropic hormone (ACTH), aminophylline, amobarbital sodium, amphotericin B, bicarbonate infusion mixtures, calcium gluconate or chloride, carbenicillin, cephalothin sodium, cefazolin sodium, chloramphenicol succinate, colistin sulfate, heparin sodium, hydrocortisone sodium succinate, iodine sodium, methicillin sodium, novobiocin, penicillin, pentobarbital, phenytoin sodium, polymyxin, prochlorperazine, sodium ascorbate, sulfadiazine, sulfisoxazole, thiopental sodium, vitamin K (sodium bisulfate or sodium salt), whole blood. 

It is soluble in alcohol but poorly soluble in water. Chloramphenicol succinate, which is used for parenteral administration, is highly water-soluble. It is hydrolyzed in vivo with liberation of free chloramphenicol. 

The usual dosage of chloramphenicol is 50-100 mg/kg/d. After oral administration, crystalline chloramphenicol is rapidly and completely absorbed. A 1-g oral dose produces blood levels between 10 and 15 mcg/mL. Chloramphenicol palmitate is a prodrug that is hydrolyzed in the intestine to yield free chloramphenicol. The parenteral formulation is a prodrug, chloramphenicol succinate, which hydrolyzes to yield free chloramphenicol, giving blood levels somewhat lower than those achieved with orally administered drug. Chloramphenicol is widely distributed to virtually all tissues and body fluids, including the central nervous system and cerebrospinal fluid, such that the concentration of chloramphenicol in brain tissue may be equal to that in serum. The drug penetrates cell membranes readily. 

An indirect enzyme immunoassay suitable for the determination of chloramphenicol and its glucuronide was developed for the analysis of urine, milk, tissue, and eggs as well (48). In this assay, chloramphenicol succinate was coupled to both bovine serum albumin and horseradish peroxidase by a mixed anhydride procedure. Unlike tissue and egg samples, urine and defatted milk could be directly analyzed, but when an ethyl acetate extraction was employed in milk analysis, the limit of detection was lowered at least 10 times. 

Strebel, L., J. Miceli, R. Kauffman, R. Poland, A. Dajani, andA. Done. 1980. Pharmacokinetics of chloramphenicol (CAP) and chloramphenicol-succinate (CAP-Succ) in infants and chilflUem.Pharmacol. Ther. 27 288-289. 

Turton JA, Andrews CM, Havard AC, Williams TC. Studies on the haemotoxicity of chloramphenicol succinate in the Dunkin Hartley guinea pig. IntJ Exp Pathol. 2002 83 225-238. 

This example demonstrates the increased power from using inbred strains compared with outbred stocks in obtaining relevant dose-response curves. The data in Table 1.2a show white blood cell (WBC) counts in four inbred strains of mice with two mice of each strain at each dose level (48 mice), treated with chloramphenicol succinate at six dose levels, these data were extracted from previously published data (25). Originally there were eight mice of each inbred strain at each dose, but in order to obtain two comparable experiments two mice of each of the four inbred strains were chosen at random at each dose level. Table 1.2b shows the WBC counts in 47 CD-I mice, with seven to nine mice per dose level in a parallel experiment conducted at the same time and under the same conditions. 

WBC counts (x 109/L) in four inbred strains of mice in response to chloramphenicol succinate (mg/kg)... 

High Pressure Liquid Chromatography. In plasma chloramphenicol and chloramphenicol succinate, detection limits 500 ng/ml for chloramphenicol and 1 pg/ml for the succinate, UV detection—R. Velagapudi et al., J. Chromat., 1982, 228, Biomed. AppL, 17, 423-428. In cerebrospinal fluid, plasma or serum sensitivity 100 to 200ng/ml, UV detection—R. H. B. Sample etal., Antimicrob. Ag. Chemother., 1979,15, 491-493. 

Pharmacokinetics. For oral use, chloramphenicol is available as the base in capsules to reduce the bitter taste and for i.v. or i.m. use as the succinate ester which is soluble. Chloramphenicol succinate is... 

Phenobarbital can increase the rate of chloramphenicol metabolism and so lead to abnormally low serum chloramphenicol concentrations. In 17 children receiving chloramphenicol succinate alone, mean peak and trough serum concentrations were 25 and 13 pg/ml respectively. In six patients phenobarbital reduced these concentrations to 17 and 7.5 pg/ml respectively (76). 

A water-soluble formulation of chloramphenicol sodium succinate is available for i.v. use. Chloramphenicol succinate is hydrolyzed to chloramphenicol in the liver. Chloramphenicol palmitate is an insoluble ester suitable for p.o. administration. Chloramphenicol palmitate is hydrolyzed to chloramphenicol in the gastrointestinal tract. Chloramphenicol (generic and veterinary labeled) is also available in a variety of tablet and capsule strengths. A long-acting formulation of florfenicol is approved for i.m. and s.c. administration to cattle. This formulation contains three carriers... 

The first two of these reactions are equally relevant for biotransformation process. Amides are often more stable to enzymatic hydrolysis than the corresponding esters with similar structures. For example, phenyl-acetate is hydrolyzed much faster than acetanilide. In addition, CarbE can hydrolyze therapeutically useful drug esters, such as chloramphenicol succinate, prednisolone succinate, procaine, and methylparaben. 

Parenteral administration Absorption of medication following an intramuscular (IM) injection is often erratic in neonates owing to their small muscle mass and an inadequate perfusion of the IM site (81,82). In a study of infants and children aged 28 days to 6 years, the IM administration of chloramphenicol succinate produced serum levels that were not significantly different from those produced in intravenous (TV) administration (83). However, the bioavailability of most drugs administered intramuscularly has not been evaluated in the pediatric population. In addition to bioavailability issues, there are other concerns specific to pediatrics with the IM administration of drugs. The volume of solution injected is directly related to the degree of pain and discomfort associated with an IM injection. Manufacturers recommendations for reconstitution of IM products often... 

An additional difficulty occurring with hemisuccinates was discovered by Sandman et al These authors, in studying the stability of chloramphenicol succinate, found an unusual partial acyl transfer reaction of the succinyl group to give a cyclic hemi-orthoester (Figure 38.6). 

Because of immature renal elimination, chloramphenicol succinate can accumulate in premature infants. Although chloramphenicol succinate is inactive, this accumulation may be the reason for an increased bioavailabifity of chloramphenicol in premature infants compared with older children. These data indicate that dose-related toxicity may result from an underdeveloped glucuronidation pathway, as well as increased bioavailability of chloramphenicol in premature infants. 

In vitro studies with gentamicin and aminophylline have shown that the delivery of these drugs may be delayed substantially depending on the flow rate and injection site. These observations were confirmed with infusion of chloramphenicol succinate and tobramycin. These studies clearly have demonstrated that the variables of intravenous drug infusion systems (e.g., flow rate. 

Nahata MC, Powell DA. Comparative bioavailability and pharmacoki- 54. netics of chloramphenicol after intravenous chloramphenicol succinate... 

Nahata MC, Powell DA, Glazer JP, et al. Effect of intravenous flow rate and infection site on in vitro delivery of chloramphenicol succinate and in vivo kinetics. J Pediatr 1981 99 463 66. 

CHLORO- mycehn) Is absorbed rapidly from the GI tract. For intravenous or intramuscular use, chloramphenicol succinate is a prodrug that is hydrolyzed by esterases to chloramphenicol in vivo. Chloramphenicol succinate is rapidly cleared from plasma by the kidneys this may reduce bioavaB-ability, since up to 30% of the dose may be excreted before hydrolysis. Poor renal fimction in the neonate and other states of renal insufficiency result in increased plasma concentrations of chloramphenicol succinate. Decreased esterase activity has been observed in the plasma of neonates and infants, prolonging time to peak concentrations of active chloramphenicol (up to 4 hours) and extending the period over which renal clearance of chloramphenicol succinate can occur. 

Aminosalicyclic acid, bacitracin, blood plasma, blood serum, methicillin salts, culture media, dextran, enzymes, gamma-globulin, hormones, streptomycin, iron dextran, lysine, casein hydrolysate, penicillin, serum hydrolysate, penicillin, serum hydrolysate, tetracycline vitamins, oleandomycin, chloramphenicol succinate salts... 

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