802 Pharmacokinetics of the rivastigmine patch Figure 1 Steady-state rivastigmine plasma levels for a typical patient following administration of the 9.5 mg ⁄ 24 h rivastigmine patch vs. 6 mg bid capsules, and the 4.6 mg ⁄ 24 h rivastigmine patch vs. 3 mg bid capsules. The model adjusts for body weight and gender (15) inhibition of plasma BuChE activity over the 24-h application period. Application sites The pharmacokinetic parameters of transdermal drug delivery can vary between patch application sites. The optimal position would offer maximum drug exposure, be easily accessible and avoid adhesion or tolerability issues (e.g. areas of hairy or sensitive skin). In a recent single-centre, single-dose, open-label, randomised-sequence, application study in 40 healthy men or women aged 40–80 years, the pharmacoki- netics, adhesion and skin tolerability of the rivastig- mine patch were assessed (17). A 9.5 mg ⁄ 24 h (10 cm2) patch was applied to one of the following ﬁve sites and worn for 24 h: upper back, chest, thigh, abdomen and upper arm. Each participant under- went ﬁve 24-h applications, one for each applica- tion site, which were separated by a 72-h washout period. Exposure levels (AUC24 h) and Cmax were shown to be the greatest when the patch was applied to the chest, upper back and upper arm (Figure 2; 123, 122 and 116 ngÆh ⁄ ml respectively). Because of the small molecular size and lipophilic nature of rivastigmine, the minimal skin thickness and subcutaneous body fat at these sites may have contributed to this ﬁnd- ing. The degree or level of adhesion was only shown to have a signiﬁcant effect on AUC24 h and Cmax when the patch was applied to the chest (p = 0.014 and 0.022 respectively). At all application sites, tmax was very slow (16–22 h) indicating smooth and con- trolled release of rivastigmine into the bloodstream. Erythema was the only type of skin reaction reported during the study and was least likely to occur when the patch was applied to the upper arm, chest and upper back. It is therefore recommended that the patch be applied to clean and dry skin on the back, upper arm or chest to obtain maximum rivastigmine expo- sure with minimal risk of skin reactions. To further ª 2009 The Authors Journal compilation ª 2009 Blackwell Publishing Ltd Int J Clin Pract, May 2009, 63, 5, 799–805