Reappraisal of the barbiturate sleeping time in mice as predictive tool for the detection of liver enzymes inhibiting drugs.

Inhibition of hepatic drug metabolizing enzymes is an important cause of clinically relevant drug interactions. A close correlation was found between influence of pentobarbital-induced sleeping time in outbred Swiss mice and hepatic drug metabolism in man for several established inhibitors, i.e. chloramphenicol, cimetidine, idrocilamide, isoniazid, metronidazole, miconazole and triacetyloleandomycin, and control drugs, i.e. baclofen, ranitidine and spiramycin. Provided that room temperature is carefully controlled, barbiturate sleeping time is a simple, inexpensive and reproducible predictive tool for the experimental detection of pharmacological agents likely to inhibit hepatic drug metabolism.