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A series of steroids including progesterone, medroxyprogesterone, norethynodrel, estrone, mestranol and ethynylestradiol have been administered either acutely of chronically, alone or in combination, to rats to test for possible effects on drug metabolism. Two hours after norethynodrel (50 mg/kg, oral) the sleeping time produced by pentobarbital was prolonged due to an increase in the level of brain pentobarbital. Medroxyprogesterone (10 mg/kg) either alone or combined with ethynylestradiol (0.018 mg/kg) and norethynodrel (10 mg/kg) combined with mestranol (0.018 mg/kg) given orally for 30 days decreased the level of brain pentobarbiral without affecting pentobarbital narcosis. Medroxy progesterone alone or combined with ethynylestradiol in the same experimental conditions increased the metabol of p-nitroanisol, aminopyrine and aniline in vitro (liver 9000 × g supernatant). Drug metabolism Progesterone Norethynodrel Ethybylestradiol Mestranol Estrone Induction Liver microsomal enzymes Contraceptive agents

Eucalyptol (1,8-cineole) given by aerosol for 4 days to rats decreases the plasma and/or brain levels of amphetamine, zoxazolamine, pentobarbital and aminopyrine given 24 hr after the last aerosol. However, the levels of plasma phenylbutazone were not affected by previous treatment with eucalyptol (1,8-cineole). Eucalyptol (1,8-cineole) pretreatment increases the rate of disappearance of plasma aminopyrine and the rate of urinary excretion of 4-aminoantipyrine, a metabolite of aminopyrine. This effect may be due to the increased rate of formation of 4-aminoantipyrine. The disappearance of aminopyrine from plasma was enhanced in 4 out of 5 volunteers submitted for 10 days to treatment with eucalyptol (1,8-cineole) aerosol.

A number of components of essential oils, such as menthol, α and β pinene, guaiacol and eucalyptol and the oil of Pinus pumilio, were studied to establish if they affect the metabolism of other drugs in rats. Eucalyptol, administered subcutaneously or by aerosol was found to increase the in vitro (9000 g) liver metabolism of aminopyrine, p-nitro-anisol and aniline and in vivo the metabolism of pentobarbital.

A linear correlation has been obtained between sleeping time and brain pentobarbital concentration 90 min after treatment of rats with 30 mg/kg i.p. of pentobarbital. Pretreatment with various drugs abolished or modified this correlation. The effect of these drugs is analysed in an attempt to identify the mechanism responsible for the modification of the pharmacological response. SKF-525A, DDT and low doses of chlorpromazine seem to act on pentobarbital sleeping time only by modifying its metabolism. Amphetamine, on the contrary, reduces the pentobarbital sleeping time by a mechanism which is not of metabolic origin. With phenobarbital pretreatment there is a modification of pentobarbital sleeping time which is the resultant of two different mechanisms: increased metabolism and increased sensitivity. Chlorpromazine at high doses, as well as diazepam, affect pentobarbital sleeping time without affecting pentobarbital metabolism.