Plasma concentrations of cytisine, a commercially available plant-based alkaloid, in healthy adult smokers taking recommended doses for smoking cessation.

1. Cytisine is a plant alkaloid that is a partial agonist for the α4β2 -nAChRs and is used as an aid to smoking cessation. To date, there are no published data on cytisine concentrations in humans following multiple dosing. The aim of this study was to determine cytisine plasma concentrations after taking recommended doses for smoking cessation and to report on adverse effects. 2. Subjects (n=10) were instructed to follow the 25-day standard dosing regimen of cytisine. Blood was collected at 0, 2, 4, 8 and 10 hours on day 1 then on subsequent visits (days 2, 3, 4, 6, 13, 14, 17, 18, 21, 22, 25 and 26) to measure plasma cytisine concentrations. Plasma concentrations were determined using a validated LC-MS method. 3. Accumulation of cytisine was observed with repeated dosing of cytisine on day 1. Mean ± SEM plasma cytisine concentration measured at 10 hours was 50.8 ± 4.7 ng/mL. Due to dose tapering, there was an overall decrease in plasma cytisine concentration over the whole treatment period. 4. Overall, cytisine was well-tolerated and adverse effects reported were minor, indicating that cytisine is safe at concentrations measured in this study. This study is registered in the Australia and New Zealand Clinical Trials Registry (ACTRN12613000002785).