Transdermal delivery of erythromycin lactobionate—implications for the therapy of gastroparesis

Abstract

Background: The treatment of many diseases may be complicated by abnormalities in gastric emptying. Gastric motor dysfunction may lead to unpredictable food and medication delivery to the small intestine, their site of absorption. Prokinetic agents improve gastric motility, but orally administered drugs are unreliably absorbed, thereby limiting their effectiveness. A method of delivering prokinetic agents which bypasses the gastrointestinal tract could lead to more effective treatment. Methods: Skin samples from rat, hairless mouse and man were placed in an in vitro diffusion chamber. The epidermal side of the skin was exposed to erythromycin lactobionate and passage of the drug across the skin sample monitored and quantitated by high‐performance liquid chromatography with UV detection. Results: Erythromycin passed across all skin types tested. Steady‐state flux across hairless mouse skin was greater than for rat, full thickness human skin and human epidermis. In the first 3 h following introduction of erythromycin lactobionate, 1.85 mg/cm2 crossed human epidermis. Given that a dose of 50 mg may exert prokinetic effects in vivo in man, increasing the patch size to ≈28 cm2 should provide therapeutic levels of drug within 3 h. Conclusions: Erythromycin lactobionate, when administered transdermally, can be delivered at levels sufficient to treat gastroparesis. This technique warrants in vivo investigation.

The Regional Distribution and Relative Frequency of Gastrointestinal Endocrine Cells in SHK‐1 Hairless Mice: An Immunohistochemical Study

“…Recently, thanks to the rapid growth of the pharmaceutical industry, the demand for animal models for use as in vivo efficacy tests has significantly increased and SKH‐1 mice have been used in skin cancer animal models ( Glaso and Wetteland, 1990; Cadi et al., 1991; Khan et al., 1992) and for in vivo efficacy testing of drugs absorbed via the skin ( Brand et al., 1997; Kommuru et al., 1999). In the latter case, drugs absorbed through the skin and working against dysfunctions of digestive tract were included.…”

Prokinetics in the Management of Functional Gastrointestinal Disorders

“…51,52 Other modes of administration are under evaluation. 53,54 Azithromycin, which has better oral biovailability than erythromycin, seems to have comparable effects. 55 It also suffers, of course from being an antibiotic and the search for a non-antibiotic but prokinetic macrolide continues.…”