The pharmacokinetic and tolerability profile of varenicline in healthy Chinese volunteers.
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.
Xiao
Y
Y
Institute of Clinical Pharmacology, First Hospital, Peking University, New York, NY, USA.
Lv
Y
Y
Zhang
X
X
Guo
Y
Y
Bergstrom
T
T
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002681:China; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011810:Quinoxalines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011978:Receptors, Nicotinic / Q000187:drug effects; D016540:Smoking Cessation / Q000379:methods; D000068580:Varenicline; D055815:Young Adult
D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D000068580:Varenicline