The cases of two patients with fulminant hepatic failure after intake of therapeutic doses (4-8 g) of paracetamol, and who were admitted to hospital for assessment for liver transplantation, are described. In both patients starvation, due to abdominal pain, nausea and vomiting or diarrhoea, was probably contributing to the toxic effect of the drug. One of the patients also had an excessive alcohol intake. Paracetamol should not be prescribed for patients with alcoholism or with low food intake.

SummaryFigdor et al.' demonstrated in 1957 that a series of structurally related pregnanes, without notable endocrine action, were anaesthetically active when administered to mice. The most active of these pregnanes was pregnanolone (3a-hydroxy-5/l-pregnane-20-one), which is a naturally occurring metabolite of progesterone, first isolated from urine of pregnant women in 1937.' The anaesthetic effect of pregnanolone has been demonstrated in several animal speciesZ3 but its lack of water solubility prevented its development in clinical practice. Pregnanolone is now prepared in a stable emulsion which may prove to be suitable for clinical use. It is solubilised in soya bean oil and emulsified in a similar way to diazepam in the form of Diazemuls.A wide species variation in toxicity and tolerance of pregnanolone emulsion was observed in preclinical studies. Administration of a single bolus injection of 40 mg/kg did not cause any (or only marginal) mortality in the mouse and the rat. No organ toxicity was noted after repeated daily intravenous injections in several species: rat 16 mglkg for 4 days and 7 mg/kg for 28 days; dog 12 mg/kg for 4 days and 3 mg/kg for 28 days; monkey 28 mg/kg for 14 days and 21 mg/kg for 28 days. Hepatic lesions restricted to the biliary system, manifested as morphological changes and increased serum enzymes, occurred after daily administration of 40-64 mg/kg for 4 days and after 14 mg/kg for 28 days in the rat. In the dog the threshold dose for hepatobiliary changes at repeated doses was about 7 mg/kg. The liver damage was clearly related to the dose, but also to the duration of the treatment, and was reversible at least in its initial state (toxicological report, not published). The anaesthetic and anticonvulsive properties of pregnanolone in animals are encouraging and very similar to those of Althesin.-This study reports the findings of a preliminary and limited clinical investigation with pregnanolone emulsion in male volunteers.

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