Ascending single dose pharmacokinetics of cytisine in healthy adult smokers

Abstract

1. Cytisine, a partial agonist for the α₄β₂-nAChR, is used as a smoking cessation medication. Cytisine’s current dosing is complex and involves taking 1.5 mg several times a day. The aim of this study was to explore the effect of dose on the pharmacokinetics and safety of cytisine after a single dose in healthy adult smokers.

2. Participants were assigned to one of three groups (n = 6 in each group) to receive a single oral dose of 1.5, 3 or 4.5 mg of cytisine. Blood samples were collected up to 24 h post dose. Pulse, blood pressure and respiratory rate were measured. Adverse effects were recorded.

3. Cytisine reached peak plasma concentration 1–2 h post dose in all participants irrespective of dose, with no dose-dependent changes in the elimination phase. Mean (SD) cytisine exposure (AUC_0–24h) were 81.9 (15.8), 181.9 (40.8) and 254.5 (48.1) ng.h/mL following 1.5, 3 and 4.5 mg, respectively.

4. Cytisine appears to have predictable pharmacokinetics following a single dose of up to 4.5 mg and may be safe given as a single 4.5 mg dose, which is threefold greater than the recommended dose taken at one time.

Trial registration: ClinicalTrials.gov identifier: NCT02585024.

Keywords:

• Cytisine
• plant alkaloid
• plasma concentration
• pharmacokinetics
• dose escalation
• safety
• smoking cessation therapy

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by the Auckland Medical Research Foundation (AMRF), New Zealand [Grant 1 1 15 011]. Cytisine capsules (Desmoxan) were supplied free of charge, from Aflofarm who had no involvement in the design, conduct or write-up of the study.