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Saffan, as a type of steroid anaesthetic, was tested to demonstrate the effect of its administration on liver function in goat. For this purpose, 40 healthy animals were divided into 4 equal groups. The 1st 2 groups were given 2 or 4 mg saffan/kg body weight (B.W.), respectively. A mixture of saffan (1 mg) and xylazine (0.1 mg)/kg B.W. was given to the 3rd group. Xylazine alone was offered to the 4th group in a concentration of 0.1 mg/kg B.W. Serum samples from all groups were analysed to measure the quantities of glucose, total protein, total and direct bilirubin as well as the activity levels of transaminases. Increased glucose levels resulted from administration of saffan which evoked more hyperglycaemia than its mixture with xylazine or xylazine alone. The hyperglycaemic effect of both doses of saffan was equivocal beyond 2 hours. The effect then differed, and glucose elevation reached the 4 fold level by 2 mg saffan and the 3 fold level by 4 mg. Total serum protein, direct and total bilirubin as well as GPT and GOT were not changed in the 4 experimental groups. This was a good indication to normal liver function in the course of administration of steroid anaesthetics to goat.

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The anaesthetic activity of pregnanolone (a metabolite of progesterone) in emulsion formulation administered intravenously to male mice was compared with that of Althesin. The loss of righting reflex for 15 seconds was used to estimate the anaesthetic effect. The mean anaesthetic dose (AD50) for the pregnanolone emulsion was 5.25 mg/kg and for Althesin, 2.8 mg/kg. The mean lethal dose (LD50) was 44 mg/kg for pregnanolone and 54 mg/kg for Althesin. The sleeping time after pregnanolone was 2.5-3.5 times longer than after Althesin in dosages above 7.5 mg/kg. No signs of pain or local reaction from injection were observed for either of the drugs. The onset of action was fast for both drugs, with only minor signs of excitation, and recovery was rapid and without excitation. The results indicate that the anaesthetic properties of pregnanolone emulsion are very similar to those of Althesin. Further studies will show whether it can fill the major vacuum left in anaesthetic practice after the withdrawal of Althesin.

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Histamine release caused by drugs and/or their solvents is a well known phenomenon. In this study, both in vivo (anaesthetized and conscious dogs) and in vitro (isolated rat peritoneal, human and guinea-pig lung mast cells) models were used. Cremophor E1 and six derivatives of 12-hydroxystearic acid were compared for their histamine releasing abilities. Although the three types of isolated mast cells responded similarly, histamine release being observed with DH (the diester of 12-hydroxystearic acid with polyethylene glycol), TN (12-hydroxystearic acid polymerized with ethylene oxide) and ME (the monoester of 12-hydroxystearic acid esterified with polyethylene glycol), the anaesthetized dog exhibited elevated blood histamine levels and clinical symptoms after administration of all the solubilizing agents, except TN and ME. The reasons for this discrepancy are not known. The addition of the drugs (Althesin or propanidid) to their solubilizing agents caused histamine release, which was not observed with the solubilizing agent alone. This is the first demonstration of an in vitro model, which copies the clinical situation, i.e. solvent does nothing but the solvent plus drug combination causes histamine release and hence adverse reactions.

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During the newborn period, there is a hight increase of the acute toxicity of two steroid anaesthetics (Hydroxydione, Althesin) given by intraperitoneal route on the rat as also an influence of hormonal conditions.

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Subacute toxicity of solvent adjuvant, alphadolone acetate and solvent, 20 per cent Cremophor solution contained in CT-1341 was studied by using rats of both sexes. Alphadolone acetate and Cremophor solution were intraperitoneally injected every day for a period of one month. Total rats tolerated to daily administration of 60 mg/kg of alphadolone acetate or of 20 ml/kg of 20 per cent Cremophor solution, without showing significant changes in body weight curves and food intake. No change was observed in blood cells and in biochemical data of blood and urine as compared with control. Rats subjected to daily administration of 60 mg/kg of alphadolone acetate presented slight patho-histological changes such as swelling of cells of the liver and kidneys, and also cell infiltration of pericapillary tissues of the lung.

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CT-1341, an intravenous anesthetic was given in various daily doses in rats for a period of one month to test the subacute toxicity. The drug was administered intraperitoneally in rats. Rats tolerated to daily administration of CT-1341 at doses of less than 1.8 ml/kg without showing other particular toxic signs than anesthesia. Main pathological findings were swelling of cells in the liver and renal tubules, and perivascular cuffing in lungs. No severe patho-histological changes were observed in any organs. Mortal cases were seen in the group of rats, in which CT-1341 was given in a daily dose of 5.4 ml/kg. A paralysis of respiratory center was suggested to be cause of death, because no severe patho-histological changes were observed in any organs of mortal rats. Survivals of this group showed no particular symptom except anesthesia, but an inhibition of the growth curve was seen in male rats only.

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Alphaxalone, an anesthetic steroid dissolved in 20% Cremophor solution was administered intraperitoneally to test the subacute toxicity (administration for one month) and chronic toxicity (administration for 3 months). In daily doses less than 8 mg/kg, alphaxalone did not show any particular toxic sign after administered for three months. Rats tolerated to daily administration of 20 mg/kg for three months, without showing severe toxic signs in body weight curve, blood cells and biochemical data obtained in blood and urine. However, some female rats receiving 50 mg/kg/day of alphaxalone, died by paralysis of respiratory center at the second day. Main histo-pathological changes induced by subacute and chronic administrations of the larger doses than 20 mg/kg, were swelling of cells in the liver and kidneys, but severe pathological changes were not seen in any organs.

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