Ethanol enemas

Citric acid, found in citrus fruits, is listed as an inhibitor, and also occurs as a reaction intermediate in the metabolic tricarboxylic acid or dtric acid cycle. Ethanol or ethyl alcohol makes an unexpected appearance as an inhibitor, as does glycerol. The ubiquitous alkaloid ingredient of coffee, better known as caffeine, is listed as an inhibitor (in fact, coffee enemas are sometimes used in folkloric cancer treatments). Creatine, a nitrogenous compound found naturally in the body, is an inhibitor, and is a known anticancer agent, for example, as used with urea in a nuxture called Carbatine. 

Two vehicles have been proposed for diazepam enemas. Both are mixtures of water and co-solvents propylene glycol - ethanol 96 % - water (4+1+5, parts by volume, pH 4.8) and glycofurol - ethanol 96 % - water (5 + 1+4, parts by volume, pH 3.6). No significant difference in irritation score was observed with healthy volunteers [52]. 

Both vehicles are also usable for some other benzodiazepines. Temazepam 10 mg in 2 mL of the glycofurol mixture, administrated to healthy volunteers, had a bioavailability equivalent to an orally administered capsule of 10 mg temazepam [4]. In this study the enema was preserved with methyl parahydroxybenzoate (0.15 %). However, a vehicle containing such high percentages of glycofurol and ethanol does not need this supplementary preservation. 

Rectal solutions have water or oil as a vehicle. If necessary to enhance the solubility of poorly soluble active substances, aqueous rectal solutirms may contain cosolvents, such as ethanol and propylene glycol. However, cosolvents and surfactants should only be used in limited amounts because of the potential irritation and the defecation reflex they may cause. For the rectal absorption of active substances from enemas the same mechanisms as for suppositories apply. A major advantage of a rectal solution over a suppository may be the fact that the active substance is already in a dissolved state which may increase the absorption rate. Increasing the volume of a rectal solution to dissolve a poorly water-soluble active substance will enhance the dissolution rate and thereby increase the absorption rate. Because of the higher volume more active substance will be dissolved and the membrane surface over which absorption occurs, is increased as well. 

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