Monitoring Transdermal Delivery of Nicotine Using In Vivo Microdialysis Sampling

gaining acceptance in pharmacological studies (1,2). Numerous studies have demonstrated the capability of microdialysis sampling in characterizing the behavior of exogenous compounds in tissues such as blood (3-6), muscle (7,8), solid tumor (9), adipose (7,10), liver (1113), and dermis (14-17). Of all the commercially available probe designs, the BAS linear tissue probe (F1) is especially suitable for use in tissues other than the brain. The usefulness and reliability of the probe has been demonstrated in muscle tissue using acetaminophen as the test compound (18). The pharmaceutical industry has recently placed increasing emphasis on dermal delivery of drug entities, especially timed-release patches. These new delivery formats, including dermal patches, have increased the sales of some established and generic drugs. Such transdermal administration of drugs has a number of advantages compared with other routes of administration. These include increased patient compliance, minimization of first-pass effect, reduction of side effects or loss of therapeutic efficiency, and avoidance of bioavailability problems. Topical application of a drug allows localized delivery of a therapeutic agent directly to or near the site of action while reducing the number and extent of systemic effects. Traditionally, pharmacokinetics of topically administered drugs are obtained in vivo by measuring and calculating drug concentrations from serial blood samples. Among the disadvantages of this approach are poor temporal resolution because of the limitations of blood sampling intervals and the extensive sample preparation required prior to analysis. Microdialysis sampling offers several features that overcome these limitations. The microdialysis process does not change the net fluid balance, so continuous sampling can be performed. Temporal resolution of the experiment is then determined by the volume of sample needed for analysis and the detection limit of the analytical method, or by the analysis time if the sampling is carried out on-line. Microdialysis is essentially a size exclusion process, so the dialysate is a protein-free aqueous sample amenable to direct injection for analysis by LC. The microdialysis probe implanted in the dermis samples from the extracellular fluid and thus reflects the local profile of the drug. Recently, this technique has been used in dermal pharmacokinetic studies in humans and animals (1417). Various linear microdialysis probe designs have been used for studies in different tissues (9,14). The excellent flexibility of the BAS linear tissue probe, along with its fiber skeleton for strength and ease of implantation, makes it wellsuited to demonstrate the potential of microdialysis sampling as a tool for the study of transdermally delivered compounds. In this report, we chose to monitor the flux of nicotine from a dermal patch intended to assist in the cessation of smoking. Monitoring Transdermal Delivery of Nicotine Using In Vivo Microdialysis Sampling