Chloramphenicol (Chloromycetin), an Antibiotic. Pharmacological and Pathological Studies in Animals 123

Gruhzit, O. M.; Fisken, Roger A; Reutner, T. F.; Martino, Edith

doi:10.1172/jci102184

Cited by 42 publications

(25 citation statements)

References 6 publications

(2 reference statements)

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“…Although neither Shelesnyak (1957) nor Spaziani & Szego ( 1959) observed damage to the uterus after the administration of antihistamines, their inhibitory action may be referable to gross damage at the biochemical level. Such a possibility is indicated by the present results and by those of Gruhzit & Fisken (1947), who found severe ulcération at the site of injection of 1 % solutions of Benadryl. In addition, in the experiments of Shelesnyak (1957), and in those of Spaziani & Szego (1959), the doses of antihistamines administered per kilogram of tissue exceed by up to twentyfold the LD 50 acute toxicity levels for the rat .…”

Section: Discussionsupporting

confidence: 71%

The Effects of Histamine on the Vaginal Epithelium of the Mouse

Martin¹

1962

Journal of Endocrinology

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Histamine dihydrochloride, administered intravaginally, was similar in action to oestrone, causing increased tetrazolium reduction, epithelial growth and cornification in the vagina. However, massive doses were required, and the ineffectiveness of histamine releasers and of various antihistamines indicated that histamine release is not involved in the response of the vagina to oestrogens. The inhibition of histamine dihydrochloride by dimethylstilboestrol indicates that oestrogenic activity is involved. However, the inactivity of the diphosphate excludes histamine itself as a weak oestrogen and suggests that histamine dihydrochloride contains minute amounts of oestrogenic contaminants.

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Section: Discussionsupporting

confidence: 71%

The Effects of Histamine on the Vaginal Epithelium of the Mouse

Martin¹

1962

Journal of Endocrinology

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“…The adult LD50 on the basis of milligrams per kilogram is 5.3 times as high as for newborns. Gruhzit et al 10 reported the LD50/14 in an unspe¬ cified strain of adult white mice, using a single I.P. injection as 1,320 mg. per kilogram.…”

Section: Resultsmentioning

confidence: 99%

The Toxicity of Chloramphenicol in Newborns Versus Adult Mice

Kent¹

1960

Arch Pediatr Adolesc Med

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Glucuronide conjugation is an important mechanism in the detoxification of chloramphenicol.1 The ability of normal adults to conjugate chloramphenicol, bilirubin, etc., with glucuronide is well established. Recent studies indicate that newborn mice, guinea pigs, and humans have a poorly developed glucuronide-conjugating mechanism.2-4 Presumably the young of other species may show a similar deficit. In such cases, drugs that are ordinarily detoxified by glucuronide conjugation thus may accumulate and more often reach toxic levels. Recent clinical reports suggest that chloramphenicol is more toxic in newborn human infants than in adults.5-7 The data on humans are limited and difficult to interpret because of inadequately controlled variables. Some experimental evaluation of chloramphenicol in the newborn versus adults therefore is desirable. MethodsForty-four litters containing a total of 394 newborn white mice of the CFW strain* were used in this study. Within 24 hours after birth, the newborns were weighed and given an injection. The weights varied from 1.14 to 2.08 gm.

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“…Its presence in the bile after an interval of two hours has been reported by Gruhzit, Fisken, Reutner, and Martino (1949), by Glazko, Wolf, and Dill (1949), and by Long, Bliss, Schoenbach, Chandler, and Bryer (1950). In the following paper some details are given of its excretion in the bile.…”

mentioning

confidence: 68%

Chloramphenicol Excretion in the Bile

Danopoulos¹,

Angelopoulos²,

Ziordrou³

et al. 1954

British Journal of Pharmacology and Chemotherapy

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It is well known that chloramphenicol is readily absorbed from the gastro-intestinal tract, and appears in the blood shortly after oral administration. Its presence in the bile after an interval of two hours has been reported by Gruhzit, Fisken, Reutner, and Martino (1949), by Glazko, Wolf, and Dill (1949), and by Long, Bliss, Schoenbach, Chandler, and Bryer (1950). In the following paper some details are given of its excretion in the bile. METHODSAbsorption from the Portal Vein by the Liver.-After a 12-hr. fast, dogs of 8 and 13 kg. were given 80-100 mg. of chloramphenicol by mouth in a sufficient quantity of water. Half an hour later the abdomen was opened under chloralose anaesthesia, and blood samples were taken from the portal and hepatic veins.Excretion in the Bile of Dogs.-After ligation and section *of the common bile duct a biliary fistula was established. The general condition of the dogs remained good for a long period, for, by licking and swallowing some of the escaping bile, they obtained a 1024 a considerable quantity by mouth. The fistula was catheterized daily with a glass 512 catheter to maintain patency. The bile flow was continuous, indicating bile of 256-hepatic and not gall-bladder origin. About E a month after operation the fistula was well m 128-organized and no bleeding followed a catheterization.O 64-In each experiment chloramphenicol u was administered by stomach tube or oral Z 32-syringe, and at the same time a rubber I catheter was inserted ihto the fistula. E 16-Bile was flowing continuously, and blood C and bile samples were collected at intervals°8-after administration. The chloramphenicol I estimations were made by the colorimetric 4-method described by Bessman and Stevens (1950).2-Excretion in Human Bile.-A dose of 1 250 mg. was given to a man weighing 46 kg. with a post-operative biliary fistula: blood and bile samples were collected after

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Chloramphenicol (Chloromycetin), an Antibiotic. Pharmacological and Pathological Studies in Animals 123

Cited by 42 publications

References 6 publications

The Effects of Histamine on the Vaginal Epithelium of the Mouse

The Effects of Histamine on the Vaginal Epithelium of the Mouse

The Toxicity of Chloramphenicol in Newborns Versus Adult Mice

Chloramphenicol Excretion in the Bile

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