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Inhibition of intestinal diamine oxidase by detergents: a problem for drug formulations with water insoluble agents applied by the intravenous route?

  • Histamine Receptors and Metabolism
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Abstract

One hundred and twenty four water-insoluble drugs were included in a study for their action on diamine oxidase (DAO) after solubilization with 61 detergents. 16 detergents were themselves not watersoluble and were not further investigated. A further 3 detergents affected the extraction procedure and 7 of the remaining 42 detergents themselves inhibited the activity of canine intestinal DAOin vitro. Only 5 detergents fulfilled all prerequisites for our DAO assay, including the solubilization of 76 water-insoluble drugs. Each of these 5 detergents had an individual range of suitability in our test system. 3/76 drugs inhibited DAO in concentrations up to 10−3 M. This result is in contrast to our study with water-soluble substances, where 16% were DAO inhibitors. Since detergents can block the enzyme which is responsible for histamine catabolism, some of the observed adverse reactions to drugs could arise because of the presence of such detergents in the formulation.

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Supported by grant of Deutsche Forschungsgemeinschaft (Lo 199/14-I).

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Sattler, J., Hesterberg, R., Schmidt, U. et al. Inhibition of intestinal diamine oxidase by detergents: a problem for drug formulations with water insoluble agents applied by the intravenous route?. Agents and Actions 20, 270–273 (1987). https://doi.org/10.1007/BF02074688

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