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Pentobarbital-induced sleeping time was found to be significantly prolonged in mice within at least 4 days following either whooping cough, tetanus, rubella or poliomyelitis vaccination. By contrast, barbital-induced sleeping time remained unaffected, These findings provide further evidence of a correlation between inhibition of liver drug metabolizing enzymes and stimulation of the immune response.

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.

Evidence suggests that stimulation of the immune response may be associated with impairment of hepatic drug metabolism. Antipyrine kinetics has therefore been determined in 12 patients on the fourth day following tetanus vaccination. Under these conditions, antipyrine plasma half-life was found to be 14.8 h. Despite the lack of control over antipyrine kinetics, these preliminary results indicate that tetanus vaccination is likely to impair the antipyrine metabolism.