L. Skovsted

INHIBITION OF DRUG METABOLISM BY CHLORAMPHENICOL

Abstract Chloramphenicol has been shown to retard the biotransformation of tolbutamide, diphenylhydantoin, and dicoumarol in man. Treatment with 2 g. of chloramphenicol for some days resulted in a rise in the concentration of tolbutamide and diphenylhydantoin in blood. The half-life values of tolbutamide, diphenylhydantoin, and dicoumarol in blood increased very considerably after chloramphenicol. A case of chloramphenicol-induced hypoglycaemic collapse in a tolbutamide-treated patient is reported.

Sulthiame (Ospolot®) as Inhibitor of Diphenylhydantoin Metabolism

The administration of sulthiame in doses of 200–800 mg daily to patients receiving diphenylhydantoin caused a rise in serum diphenylhydantoin after 1 week of combined treatment. In the doses mentioned above sulthiame increases the half‐life in the blood of injected radioactive diphenylhydantoin. Sulthiame apparently inhibits the metabolism of diphenylhydantoin in the liver, but it has not yet been possible to elucidate the mode of this inhibition.

The influence of disulfiram on the half life and metabolic clearance rate of diphenylhydantoin and tolbutamide in man

SummaryDiphenylhydantoin (DPH) and tolbutamide serum levels were studied in ten volunteers before and after 4 days of disulfiram treatment. The mean DPH half life incresed significantly from 11.0±1.2 h to 19.0±3.3 h, and the mean DPH metabolic clearance rate decreased significantly from 51.2±17.2 ml/min to 33.9±12.0 ml/min during medication. No significant changes in the half life or metabolic clearance rate of tolbutamide was observed.