Device for Acamprosate Transcutaneous Delivery to Reduce Alcohol Consumption.

DESCRIPTION (provided by applicant): Alcohol dependence is a chronic disorder with genetic, psychosocial, and environmental underpinnings. Alcohol's societal impact is widespread; it is estimated that there are 17.6 million individuals who abuse or depend on alcohol in the United States. (Grant et al, 2004). Alcohol dependence is considered the third leading preventable cause of death in the United States after cigarette smoking and obesity, attributing to more than 100,000 deaths per year. Overall, the annual economic cost of alcohol abuse, in the United States alone, exceeds $185 billion (Harwood, 2000). In the past decade, there has been increasing interest in the use of pharmacotherapies to treat alcohol dependence (Swift, 1999; Anton and Swift, 2003). Acamprosate/Campral (acetyl calcium homotaurinate) is a new, FDA-approved medication that promotes alcohol abstinence and can potentially reduce the impact of alcohol dependence. However, one of the problems with acamprosate is its poor bioavailability, as only 11% of an oral dose is absorbed. Moreover, the low bioavailability necessitates thrice daily dosing, which can reduce medication adherence and result in less medication dose. Improving acamprosate bioavailability can improve its effectiveness. In animal models of ethanol self- administration, acamprosate treatment has been shown to decrease ethanol intake (Boismare et al., 1984) but not food or fluid intake (Czachowski et al., 2001; Naassila et al., 1998) when administered parenterally which is the preferred method of administration for animal models, thus eliminating the problems with oral bioavailability and gastro-intestinal side effects. If a parenteral administration method could be applied to humans, it could significantly improve the effectiveness of acamprosate. A unique, interdisciplinary team of experts from academia and industry will develop a wearable, non-invasive delivery device, with a high expected bioavailability for acamprosate, during Phase 1. By releasing a controlled amount of solution of acamprosate from a pressurized reservoir, through the skin's stratum corneum, non-invasively via a hollow microneedle array, the acamprosate will bypass the skin barrier, and diffuse directly into the blood, via the skin capillaries. Thus, the transcutaneous, flow-modulated, microneedle array-enhanced delivery of acamprosate is expected to increase up to 5-7 times its poor (11%) oral bioavailability, so that 55-80% of a dose is absorbed in a rat-model study.