Rabbit skin, enhanced absorption

Dermac SR-38 is one of a series of oxazolidinones, cyclic urethane compounds, evaluated as transdermal enhancers. The compound was designed to mimic natural skin lipids (such as ceramides), to be nonirritating, and to be rapidly cleared from the systemic circulation following absorption. In animal and human safety studies, Dermac SR-38 demonstrated a good skin tolerance (no observed irritancy or sensitization at levels of 1-10 wt% moderate to severe irritation in rabbit at 100%), and a low degree of acute toxicity (LD50(rat oral) > 5.0g/kg). The compound was evaluated for its ability to enhance the human skin permeation of diverse drugs from dermal and transdermal delivery systems. Data for minoxidil indicated an enhancer concentration-dependent effect for permeation enhancement. Dermac SR-38 was also found to enhance the skin retention of both retinoic acid when applied in Retin A cream, and dihydroxyacetone when applied in a hydrophilic cream. ... 

Hexachlorophene is well absorbed orally and dermal-ly and through mucosal surfaces. In rats, up to 55% of dermally applied hexachlorophene is absorbed in 24 h. Dermal absorption is enhanced by dimethylsulf-oxide and dermatitis or skin abrasions. Placental transfer has been demonstrated in rats. Hexachlorophene is converted to hexachlorophene-jS-o-glucuro-nide in the rat and rabbit. Some hexachlorophene has been found in the blood and adipose tissue. Hexachlorophene was administered intraperitoneally to rats and rabbits excretion was slow and most (48-83%) was excreted unchanged in the feces. Hepatic function is an important determinant in the removal of hexachlorophene. In a rat study, within 3h after administration, 50% was excreted in the bile. Rats given intraperitoneal doses excreted 5 % of the dose in the urine and none as CO2 more than 70% of the material was excreted in feces. 

Alcohol also has the potential for enhancing the toxicity of nitrobenzene however the toxicokinetic mechanism is not known. It is clear, however, that alcohol does not simply enhance the absorption of nitrobenzene. When alcohol was given orally and nitrobenzene is given intravenously, there was increased toxicity in rabbits. Alcohol also enhanced the neural toxicity of nitrobenzene in rabbits when nitrobenzene was applied to the skin (Matsumaru and Yoshida 1959). 

There are few smdies on the in vivo efficacy and irritancy of terpenes used as an enhancer in percutaneous absorption. The percutaneous absorption-promoting effect and skin irritancy of cyclic monoterpenes were investigated in rats and with rabbits, respectively (Okabe etal., 1990). Plasma concentration of the drug (ketoprofen) markedly increased with the addition of the hydrocarbons of cyclic monoterpenes such as trans- -methane and d-limonene. Irritancy of cyclic monoterpenes in rabbits was evaluated using the Draize scoring method. No skin irritation was observed when ethanol-containing hydrocarbons of cyclic monoterpenes (trans-p-menthane and d-limonene) were applied to dorsal skin. 

NMP was shown to enhance the percutaneous absorption of mefenamic add and bupranolol in vivo in rabbits (Naito et al., 1985 Ogiso et al., 2001). In humans, NMP and 2-pyrrolidone were shown to cause skin irritation while increasing the bioavailabihty of betamethasone-17-benzoate (Barry etal., 1984 Bramet etal., 1985). Even though they are effective, the skin irritation prevents the widespread use of these agents in transdermal systems (SasaM et al., 1990a). 

Rabbit serum and bovine serum albumin had no effect on the integrity of the barrier, but they were also less effective in increasing cinnamyl anthranilate absorption than oleth 20. A methanol-water solution and 6> octoxynol 9 (Triton X-100, Rohm and Haas Co., Philadelphia, PA) were equal to or superior to (>% oleth 20, but significant damage to the skin was Indicated by the increased cortisone permeation. A 6% solution of poloxamer 188 in the receptor resulted in slight enhancement of both cinnamyl anthranilate and cortisone permeation. 

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