Cardiovascular effects of buccal exposure to dermal nicotine patches in the dog: a comparative evaluation.
OBJECTIVE
Safety concerns have been raised over the possible effects of inappropriate exposure to transdermal nicotine patches. This study was initiated to determine whether placement of these products into the mouth could affect cardiovascular function.


METHODS
In a series of 10 anesthetized beagle dogs, Nicoderm, Habitrol, ProStep I (Intact), ProStep D (Damaged) transdermal nicotine products or the Skoal Bandit smokeless tobacco plug were placed in the buccal cavity for 5 minutes. Systemic arterial blood pressure and the electrocardiogram were monitored for up to 90 minutes after exposure with blood samples at intervals during the first 10 minutes for plasma nicotine concentration.


RESULTS
The systolic and diastolic arterial blood pressures and heart rate increased within 2 minutes of buccal exposure to either the intact or the damaged ProStep nicotine product. Ventricular arrhythmias were observed in 6 of 10 dogs exposed to the intact patch and 7 of 10 dogs exposed to the damaged patch during the period of maximal cardiovascular response. Modest increases in systemic blood pressure and heart rate were seen with the Nicoderm and Habitrol products but not with the Skoal Bandit. The increases in systemic arterial pressure and heart rate occurring after exposure to ProStep were significantly more severe than those observed after Nicoderm and Habitrol. Mean peak nicotine levels of 9.8 microg/mL (ProStep 1), 5.4 microg/mL (ProStep D), 3.4 microg/mL (Habitrol), 2.5 microg/mL (Nicoderm), and 0.12 microg/mL (Skoal Bandit) were detected within 2 to 10 minutes after buccal placement of the product.


CONCLUSIONS
Certain transdermal nicotine patches, when applied to a nondermal site such as the buccal cavity for a short period (5 minutes) can rapidly provoke significant cardiovascular alterations (hypertension, tachycardia, and ventricular arrhythmias). The magnitude of the cardiovascular responses occurring after buccal exposure to a product such as ProStep could pose a risk to susceptible individuals.
Herman
E H
EH
Division of Applied Pharmacology Research, Center for Drug Evaluation and Research, Food and Drug Administration, Laurel, Maryland 20708, USA. hermaneh@cder.fda.gov
Vick
J A
JA
Strong
J M
JM
Parker
R J
RJ
Geyer
H M
HM
Kramer
E D
ED
Higgins
K M
KM
Sistare
F D
FD
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004562:Electrocardiography; D008401:Gas Chromatography-Mass Spectrometry; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D018722:Nicotinic Agonists / Q000009:adverse effects*; D010947:Plants, Toxic; D014030:Tobacco, Smokeless / Q000009:adverse effects
D018722:Nicotinic Agonists; D009538:Nicotine