title: Effect of exercise on transdermal nicotine release in healthy habitual smokers.
abstract: OBJECTIVE
  Transdermal nicotine patches have become a frequently prescribed tool in smoking cessation programs during the past years. However, there is circumstantial evidence that transdermal nicotine release substantially varies with physical activity producing toxic plasma concentrations that may account for severe adverse events.
  
  
  METHODS
  We, therefore, compared nicotine release from two different transdermal nicotine systems (TDNS) at rest and during strenuous physical activity in a two-period crossover study in healthy smokers (n = 10). The subjects were randomly assigned to receive either 21 mg/day of formulation A or B on study Day 1 and 2. Patches were applied eight hours before starting standardized physical activity, and nicotine concentrations were measured in plasma and topically in the tissue layers underneath the application site by microdialysis.
  
  
  RESULTS
  There was no difference between groups in the mean values for area under the time-concentration curve at rest from 0 - 8 hours AUC(0-8) (p < 0.799) and during exercise from 8 - 11 hours AUC(8-11) (p < 0.878). C(max) values between groups with C(max) values of 16.4 +/- 9.5 ng/ml and 16.0 +/- 10.7 ng/ml at rest (p < 0.919, NS) and 10.05 +/- 6.8 ng/ml and 10.2 +/- 6.9 ng/ml (p < 0.959, NS) during exercise did not differ significantly. Nicotine tissue concentrations increased two-fold during exercise versus baseline (p < 0.878). Skin blood flow increased significantly during exercise compared with baseline (p < 0.001). No adverse events were observed.
  
  
  CONCLUSIONS
  The present study provides evidence that transdermal nicotine release from TDNS increases during exercise. However, this increase has no significant effect on overall plasma pharmacokinetics. Our pharmacokinetic data further indicate that the two TDNS formulations are equivalent during conditions of rest and exercise.
authors.affiliation: Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, University of Vienna Medical School, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Bur
authors.forename: C
authors.initials: C
authors.lastname: Joukhadar
authors.forename: N
authors.initials: N
authors.lastname: Klein
authors.lastname: Herkner
authors.forename: G
authors.initials: G
authors.lastname: Mitulovic
authors.forename: R
authors.initials: R
authors.lastname: Schmid
authors.forename: E
authors.initials: E
authors.lastname: Agneter
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.forename: M
authors.initials: M
authors.lastname: Brunner
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D018592:Cross-Over Studies; D015444:Exercise; D006801:Humans; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism*
chemical_list: D009538:Nicotine