PHARMACOKINETIC CHARACTERIZATION OF TRANSDERMAL DELIVERY SYSTEMS

The key aspects of the pharmacokinetics of transdermal delivery system s including time lag, steady-state plasma levels and decline phase are illustrated in this review. The 7 currently marketed transdermal syst ems [nitroglycerin (glyceryl trinitrate), estradiol, clonidine, fentan yl, nicotine, scopolamine (hyoscine) and estradiol/norethisterone acet ate] are discussed, as are systems in development. Single-dose absolut e bioavailability studies characterise the period of onset, the steady -state plateau and the declining phase, and typify transdermal deliver y. More complex temporal profiles result from interactions with enhanc ers or removal of the system before steady-state conditions are achiev ed. Clinically these systems are used to achieve multiple peak serum e stradiol concentrations after application of transdermal estradiol, an d an initial peak systemic concentration of testosterone after applica tion of transdermal testosterone. Multiple-dose, dose proportionality and skin site bioequivalence studies are needed for the full pharmacok inetic characterisation of a transdermal delivery system. The relation ship of system design to variability is discussed. Although the data a re limited, population factors, cutaneous metabolism and tolerance all appear to influence the disposition of drugs administered transdermal ly. For example, the route of delivery influences which nitroglycerin metabolite predominates. Futhermore, as a result of tolerance to nitra tes, a transdermal delivery system must be removed for 8 to 12 hours f or optimal effect. Therefore, transdermal delivery systems, designed o n the basis of pharmacokinetic principles and concentration-effect rel ationships, have the potential to provide optimal therapy for the trea tment of some conditions.