All participants gave their informed consent. Tolerance and safety of the treatments applied in the study was determined by a clinician assessing withdrawal and other adverse events. The study was carried out as a pilot trial for GlaxoSmithKline Vemurafenib molecular weight Consumer Healthcare (GSKCH) according to protocol A2410337. GSKCH participated in the writing of the protocol, but had no possibility of influencing the data. Plasma concentration pharmacokinetic parameters, total drug transport during the study period, and maximal drug concentration achieved were log-transformed and analysed using a linear mixed-effects analysis of variance (ANOVA)

with factors for subject (as a random effect), period, and treatment. The residual mean square from the ANOVA was used to construct confidence intervals for the difference between treatments and then expressed as a ratio. Time for maximal concentration (Tmax) was analysed using the Wilcoxon’s rank sum test for a 2×2 crossover design, taking sequence into account. Median difference in Tmax was calculated using the Hodges–Lehmann one sample method. Subjects with data from one period only were excluded from the Tmax Dolutegravir analysis. Both muscular and subcutaneous concentrations of diclofenac were negligible in the majority of subjects, with 80% showing

values below the sensitivity limit (0.5 ng/ml), data not shown. Iontophoretic application caused a maximal plasma concentration of 3.4±0.5 ng/ml (±SEM) with a plateau from 2 h application, while gel alone showed a similar pattern but only lead to a maximal concentration of 0.4 ng/ml±0.05 ng/ml (±SEM) which is below the limit for analysis sensitivity (Fig.

1, Table 1). Maximal concentration Interleukin-2 receptor and total diclofenac delivered to plasma was significantly higher for the iontophoretically applied drug than the standard gel application. There was no difference in time for reaching maximal concentration with the two methods, and with the clear plateau in both cases, a steady state appears to have been reached in both (Fig. 1). One subject in the iontophoresis group was withdrawn due to flu-like symptoms which was associated with the microdialysis procedure. Four subjects, all in the iontophoretic patch group, developed blisters of 0.1–0.5 cm in diameter and one also developed a skin rash at the patch site. In the present study, it was not possible to detect a meaningful diclofenac concentration in the underlying tissues after one patch application. This was the case for both iontophoresis and passive delivery. The iontophoretic patch did show a facilitated transport of diclofenac over the skin. With both application methods diclofenac was seen to reach the circulation, but a standard gel application only caused a plasma concentration at the limit of detection, while iontophoretic application gave a comparably higher and measurable plasma concentration.