PMID- 19243716
OWN - NLM
STAT- MEDLINE
DCOM- 20090407
LR  - 20220408
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 31
IP  - 1
DP  - 2009 Jan
TI  - Pharmacokinetics, safety, and tolerability of varenicline in healthy adolescent 
      smokers: a multicenter, randomized, double-blind, placebo-controlled, 
      parallel-group study.
PG  - 177-89
LID - 10.1016/j.clinthera.2009.01.003 [doi]
AB  - BACKGROUND: Varenicline is approved as an aid to smoking cessation in adults aged 
      > or =18 years. OBJECTIVE: The goal of this study was to characterize the 
      multiple-dose pharmacokinetics, safety, and tolerability of varenicline in 
      adolescent smokers. METHODS: This multicenter, randomized, double-blind, 
      placebo-controlled, parallel-group study enrolled healthy 12- to 16-year-old 
      smokers (> or =3 cigarettes daily) into high-body-weight (>55 kg) and 
      low-body-weight (< or =55 kg) groups. Subjects were randomized to receive 14 days 
      of treatment with a high dose of varenicline, a low dose of varenicline, or 
      placebo. The varenicline doses in the high-body-weight group were 1 mg BID and 
      0.5 mg BID; the varenicline doses in the low-body-weight group were 0.5 mg BID 
      and 0.5 mg once daily. The apparent renal clearance (CL/F) and volume of 
      distribution (V/F) of varenicline and the effect of body weight on these 
      parameters were estimated using nonlinear mixed-effects modeling. RESULTS: The 
      high-body-weight group consisted of 35 subjects (65.7% male; 77.1% white; mean 
      age, 15.2 years). The low-body-weight group consisted of 37 subjects (37.8% male; 
      48.6% white; mean age, 14.3 years). The pharmacokinetic parameters of varenicline 
      were dose proportional over the dose range from 0.5 to 2 mg/d. The CL/F for a 
      70-kg adolescent was 10.4 L/h, comparable to that in a 70-kg adult. The estimated 
      varenicline V/F was decreased in individuals of small body size, thus predicting 
      a varenicline C(max) approximately 30% greater in low-body-weight subjects than 
      in high-body-weight subjects. In high-body-weight subjects, steady-state 
      varenicline exposure, as represented by the AUC(0-24), was 197.0 ng . h/mL for 
      varenicline 1 mg BID and 95.7 ng . h/mL for varenicline 0.5 mg BID, consistent 
      with values reported previously in adult smokers at the equivalent doses. In 
      low-body-weight subjects, varenicline exposure was 126.3 ng . h/mL for 
      varenicline 0.5 mg BID and 60.1 ng . h/mL for varenicline 0.5 mg once daily, 
      values at the lower end of the range observed previously in adults at doses of 1 
      mg BID and 0.5 mg BID, respectively. Among high-body-weight subjects, adverse 
      events (AEs) were reported by 57.1% of subjects in both the high- and low-dose 
      varenicline groups and by 14.3% of subjects in the placebo group; among 
      low-body-weight subjects, AEs were reported by 64.3%, 73.3%, and 12.5% of 
      subjects in the high-dose varenicline, low-dose varenicline, and placebo groups, 
      respectively. The most common AEs were nausea, headache, vomiting, and dizziness. 
      Psychiatric AEs that were considered treatment related included abnormal dreams 
      in 2 subjects and mild, transient anger in 1 subject. Of the AEs reported by > or 
      =1 subject in any treatment group, > or =92% were mild in intensity. No subject 
      discontinued the study because of an AE. CONCLUSIONS: Varenicline steady-state 
      exposure in study subjects weighing >55 kg was similar to that observed 
      previously in adults. The body-weight effect on varenicline pharmacokinetics, 
      which resulted in higher exposure in individuals of smaller body size (< or =55 
      kg), was adequately offset by administration of half the varenicline dose 
      recommended in adults. Varenicline was generally well tolerated during the 14-day 
      treatment period. Clinical Trials Identification Number: NCT00463918.
FAU - Faessel, Helene
AU  - Faessel H
AD  - Pfizer Global Research and Development, New London, Connecticut, USA. 
      helene.m.faessel@pfizer.com
FAU - Ravva, Patanjali
AU  - Ravva P
FAU - Williams, Kathryn
AU  - Williams K
LA  - eng
SI  - ClinicalTrials.gov/NCT00463918
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Benzazepines)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (Quinoxalines)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (nicotinic receptor alpha4beta2)
RN  - W6HS99O8ZO (Varenicline)
SB  - IM
MH  - Adolescent
MH  - Area Under Curve
MH  - Benzazepines/administration & dosage/adverse effects/*pharmacokinetics
MH  - *Body Weight
MH  - Child
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Nicotinic Agonists/administration & dosage/adverse effects/*pharmacokinetics
MH  - Nonlinear Dynamics
MH  - Quinoxalines/administration & dosage/adverse effects/*pharmacokinetics
MH  - Receptors, Nicotinic/drug effects
MH  - Smoking Cessation/*methods
MH  - Tissue Distribution
MH  - Treatment Outcome
MH  - Varenicline
EDAT- 2009/02/27 09:00
MHDA- 2009/04/08 09:00
CRDT- 2009/02/27 09:00
PHST- 2008/12/04 00:00 [accepted]
PHST- 2009/02/27 09:00 [entrez]
PHST- 2009/02/27 09:00 [pubmed]
PHST- 2009/04/08 09:00 [medline]
AID - S0149-2918(09)00017-4 [pii]
AID - 10.1016/j.clinthera.2009.01.003 [doi]
PST - ppublish
SO  - Clin Ther. 2009 Jan;31(1):177-89. doi: 10.1016/j.clinthera.2009.01.003.