Source
Institute of Clinical Pharmacology, First Hospital, Peking University, New York, NY, USA.
Abstract
OBJECTIVE:
Varenicline is a selective, nicotinic alpha4beta2 acetylcholine receptor partial agonist that has been licensed as a smoking cessation drug in more than 70 countries worldwide. The current study was conducted in order to evaluate its pharmacokinetic (PK) properties and tolerability in healthy volunteer Chinese smokers.
METHODS:
This was an open-label, non-randomized study conducted over 17 days at a single center in China. Male and female subjects (18 - 45 years old) received a single, 1 mg dose of varenicline on days 1 and 10 as well as 1 mg varenicline twice daily (12-h dosing interval) on Days 4 - 9.
RESULTS:
A total of 14 subjects (50% male) received varenicline as per study protocol for 8 days. The mean maximum plasma concentration of varenicline (Cmax) was 1.93-fold larger at steady state (reached on Day 8, after 4 days of repeat dosing) than following a single dose, showing accumulation of varenicline on repeat administration. Median values of tmax (time of occurrence of Cmax) were similar for both dosing regimens (3.0 and 2.5 h following single and multiple dosing, respectively). The mean elimination half-life following single and multiple dosing was 15.2 and 18.3 h, respectively. There was no evidence of time- or concentration-dependence in the PK of varenicline upon repeat dosing as the ratio of the area under the plasma concentration vs time curve (AUC) from time 0 - 12 h at steady state to the AUC from time 0 - 8 on Day 1 was nearly 1. The 2-sided 95% confidence intervals for this comparison included 1, demonstrating the linearity of the PK of varenicline for the single and multiple doses. Varenicline was safe and well-tolerated, adverse events were mild in severity and there were no abnormal laboratory tests.
CONCLUSIONS:
Varenicline 1 mg twice daily was safe and well-tolerated in a cohort of healthy male and female, 18- to 45-year-old Chinese smokers and demonstrated PK properties that were stable and reproducible and similar to those observed previously in Western subjects.