Several preparations of Cremophor E1, several of other non-ionic detergents and several components of Cremophor E1 were tested for their histamine-releasing capacity in dogs. Lutensol AP 10 and a derivative of 1,2-propylenglycol were ineffective, but showed excellent properties as detergents. Thus the histamine-releasing capacity was not necessarily combined with the tenside effect of the surfactants. Oleic acid found in Tween 80 as well as in Cremophor E1 seems to be the most effective constituent, but the alcohol seems also to be important for the histamine-releasing capacity. The development of a non-toxic solubilizer for lipophilic drugs seems of considerable clinical interest.

No abstract

Using a recently established porcine model, it was clearly shown that oral histamine administration is extremely dangerous in the presence of diamine oxidase (DAO) blockade. Due to the severity of the symptoms (20% death) and the clinical relevance, further interest has been focussed on strategies to prevent or alleviate food induced histaminosis. In a randomized controlled trial, 10 pigs under DAO blockade were challenged with oral histamine (60 mg). Half of these animals received a prophylactic premedication with a combination of H1- and H2-receptor antagonists. As expected, all animals developed a massive increase in plasma histamine levels, with significantly higher values in the control group (median: 123 ng/ml) compared to the antihistamine group (median: 32 ng/ml). In contrast, clinical symptoms were only observed in the control group. The maximum fall in mean arterial pressure (hypotension) was 60 mmHg (median for control group) but only 15 mmHg (median) under antihistamine pretreatment. These results firstly provide further evidence for the causal role of histamine in the new disease concept and secondly enable us to investigate appropriate therapeutic measures for patients at risk.

Histamine concentrations in canine whole blood and plasma were determined under several pharmacological, pathophysiological, and clinical conditions using fluorometric methods.The specificity of the assay for whole-blood histamine was investigated by comparing 3 purification procedures for the isolation of histamine from whole blood including butanol extraction (Shore), ion-exchange chromatography on Dowex 50 W-X 8, and the combination of these 2 methods (Lorenz). Histamine in whole blood was identified in analytical and preparative samples by fluorescence spectra, thin-layer chromatography, degradation by diamine oxidase from pig kidney and inactivation by histamine methyltransferase from guinea-pig brain as well as by biological tests on the isolated guinea-pig ileum. Since butanol extraction resulted in significantly higher 'histamine' values than the other two purification procedures, ionexchange chromatography on Dowex 50 was recommended as the method of choice for the specific determination of histamine in doffs whole blood.Normal values of histamine concentrations in canine plasma were tentatively estimated. They depended on the time between pretreatment of the animals (anaesthesia, operation) and the collection of blood and showed an approximately logarithmic normal distribution. The median, the lower/upper quartiles and the range of the plasma histamine levels obtained 30 minutes after the end of pretreatment were 0.2, 0-0.4 and 0-1.2 ng/ml, respectively. Nearly 50 % of the values were zero (below 0.1 ng according to the sensitivity of the method), only 1 ~ of them exceeded slightly 1 ng/ml. Thus histamine release by drugs or by other medical treatments was only stated, when plasma histamine levels exceeded 1 ng/ml and decreased in a way to give an elimination carve of approximately first-order kinetics (Bateman function).Histamine concentrations in dog's whole blood showed approximately a logarithmic normal distribution. The median, lower/upper quartiles and range were 47, 34/75 and 13-209 ng/ml respectively.