The Enzymatic Hydrolysis of Chloramphenicol (Chloromycetin)

Smith, G. N.; Worrel, Cecilia S.; Lilligren, Betty L.

doi:10.1126/science.110.2856.297

Cited by 18 publications

(8 citation statements)

References 6 publications

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“…it was shown that traces of a degradation product, p-nitrobenzoic acid, were present in liver and meat samples of animals slaughtered 18 h after treatment. The metabolic transformation of CAP involves several metabolites (Smith et al, 1949;Smith & Worrel, 19 50). Evidence has been presented suggesting that metabolites of CAP, DH-CAP, NPAP and NO-CAP.…”

Section: Discussionmentioning

confidence: 99%

Bioavailability, pharmacokinetics and residues of chloramphenicol in the chicken*

Anadón

Bringas

Martínez-Larrañaga

et al. 1994

Vet Pharm & Therapeutics

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The pharmacokinetic properties of chloramphenicol were determined in broiler chickens after two single oral doses (30 and 50 mg/kg body weight) and after a single intravenous (i.v.) dose (30 mg/kg body weight). After oral and i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. After oral administration (30 and 50 mg/kg), chloramphenicol was absorbed rapidly (time to maximal concentration of 0.72 or 0.60 h) and eliminated with a mean half-life (t1/2 beta) of 6.87 or 7.41 h, respectively. The bioavailability was 29% at 30 mg/kg chloramphenicol and 38% at 50 mg/kg chloramphenicol. Concentrations greater than 5 micrograms/ml were achieved at 15 min and persisted up to 2 or 4 h post-administration, respectively. Statistically significant differences between the two routes of administration were found for the pharmacokinetic variables, half-lives of both distribution and elimination phases (t1/2 alpha, t1/2 beta) and apparent volume of distribution [Vd(area)]. The mean t1/2 beta of chloramphenicol and i.v. administration was 5.23 h. Chloramphenicol was extensively metabolized into dehydrochloramphenicol (DH-CAP), nitrophenylaminopropanedione (NPAP) and nitroso-chloramphenicol (NO-CAP) derivatives. Residues of chloramphenicol (CAP) and the three metabolites DH-CAP, NPAP and NO-CAP in kidney, liver and muscle were measured in chickens that received an oral dose of 50 mg/kg once daily for 4 days. The results indicate that CAP and DH-CAP residues were cleared slowly and were at or below the detection limit of 0.005 microgram/ml within 12 days after dosing. However, at the time of slaughter (12 days), the NPAP and NO-CAP residues were detected in the tissue.

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Section: Discussionmentioning

confidence: 99%

Bioavailability, pharmacokinetics and residues of chloramphenicol in the chicken*

Anadón

Bringas

Martínez-Larrañaga

et al. 1994

Vet Pharm & Therapeutics

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“…Other bacteria, including strains of Escherichia coli and species of Bacillus, reduce the nitro group of chloramphenicol (Smith & Worrel, 1949, 1950b; Merkel & Steers, I 953). However, the ability to reduce chloramphenicol is inducibly acquired by these organisms (Merkel & Steers, 1953) and, at least in strains sensitive to chloramphenicol, its reduction was a very slow process.…”

Section: Discussionmentioning

confidence: 99%

The Ferredoxin-dependent Reduction of Chloramphenicol by Clostridium acetobutylicum

O'Brien

Morris

1971

Journal of General Microbiology

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S U M M A R YChloramphenicol did not inhibit growth and protein synthesis when added ( IOO ,ug./ml.) to growing cultures of Clostridium acetobutylicum, even though the organism was sensitive to this antibiotic in plate assay. This paradox was explained by the finding that chloramphenicol was rapidly reduced and thus detoxified by actively growing cultures. Cell-free extracts of C. acetobutykum reduced the aryl nitro group of chloramphenicol via a ferredoxin-dependent enzymic reaction for which pyruvate was the most effective primary electron donor. A number of other aryl nitro-compounds were similarly reduced.

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“…Bacterial enzymes hydrolyze chloram phenicol to dichloroacetic acid and XXIII. It is not attacked by crystalline pepsin or chymotrypsin but is hydrolyzed slowly by papain and trypsin (126). Actively growing bacteria reduce the nitro group to an amine (127).…”

Section: Cahsochoh·cb(nh2)·ch20hmentioning

confidence: 99%