Pharmacologic implications of alterations in the metabolism of chloramphenicol
| Autor: | John Alvin, Balwant N. Dixit |
|---|---|
| Rok vydání: | 1974 |
| Předmět: |
Time Factors
Glucuronates Hexobarbital Pharmacology Biochemistry Benzoates chemistry.chemical_compound In vivo Acetamides Phenethylamines medicine Animals Sulfones Glucuronidase Chloramphenicol Metabolism Fasting Thiamphenicol Glucuronic acid Anti-Bacterial Agents Rats chemistry Liver Microsome Spectrophotometry Ultraviolet Glucuronide Sleep medicine.drug Toluene |
| Zdroj: | Biochemical pharmacology. 23(1) |
| ISSN: | 0006-2952 |
| Popis: | In the present study, it was shown that in rats the glucuronide conjugation of chloramphenicol was reduced by 18- to 24-hr fasting and by pretreatment with o - and p -toluic acids. This was reflected in the increased availability of chloramphenicol to produce liver microsomal enzyme inhibition. Eighteen- to 24-hr fasting and administration of o - and p -toluic acids delayed the disappearance of chloramphenicol from the plasma and from the liver and reduced the levels of chloramphenicol glucuronide in the plasma and in the liver tissue. These changes in the inactivation profile were accompanied by potentiation of chloramphenicol-induced prolongation of hexobarbital sleeping time. In fasted rats, glucose administration antagonized the changes observed in chloramphenicol metabolism and its effect on hexobarbital sleeping time. Pretreatment with o -toluamide, which is not conjugated with glucuronic acid, did not have a significant effect on glucuronide conjugation of chloramphenicol. It was also shown that thiamphenicol-induced inhibition of liver microsomal enzymes in vivo , measured in terms of its effect on the prolongation of hexobarbital sleeping time, was not affected either by fasting or by administration of o - and p -toluic acids. Thiamphenicol, an analog of chloramphenicol, is not metabolized by glucuronide conjugation, but is excreted unchanged. These observations indicate that the potentiation of chloramphenicol-induced prolongation of hexobarbital sleeping time in fasted and in o - or p -toluic acid-treated rats was due to the availability of higher amounts of chloramphenicol producing a greater degree of microsomal inhibition. |
| Databáze: | OpenAIRE |
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