Absorption and Adverse Effects following Topical and Oral Administration of Three Transdermal Nicotine Products to Dogs

Cardiovascular Effects of Buccal Exposure to Dermal Nicotine Patches in the Dog: A Comparative Evaluation

“…A dog model was utilized because the cardiovascular and other responses to nicotine and the bioavailability of nicotine in this animal are similar to that found in humans (6). Orally administered Habitrol and Nicoderm patches were intentionally damaged to mimic mastication of the patch whereas ProStep was not altered.…”

“…Matsushima et al (6) conducted a study in dogs to compare the effects of three different transdermal nicotine products that were either swallowed or applied topically. A dog model was utilized because the cardiovascular and other responses to nicotine and the bioavailability of nicotine in this animal are similar to that found in humans (6).…”

“…In a clinical study with three different dermal nicotine products (Habitrol  , Nicoderm  , and ProStep  ) severe cardiovascular alterations were observed in a human subject shortly after oral exposure to the ProStep nicotine patch (5). Little difference in overt effects was noted in beagle dogs following nondermal exposure to these same products (6). At present such studies have provided only limited information concerning the risk associated with oral exposure to these three transdermal nicotine products.…”

NIOSH skin notation (SK) profile: nicotine [CAS No. 54-11-5].

“…In mice, Shah et al [1981] observed that the geometric mean percentage penetration of radiolabeled nicotine (1 mg per kilogram body weight [mg/kg]) increased with duration of exposure, recording values of 5.2% (1 min), 27.9% (5 min), 59.5% (15 min), 71.5% (60 min), and 90.7% (480 min). Matsushima et al [1995] evaluated dermal absorption of nicotine in dogs and found that topically administered nicotine patches at dosages of 1 to 2 mg/kg for 24 hours resulted in a maximum plasma concentration of 43 ng/mL.…”

“…Toxicokinetic data on humans in vivo [Benowitz et al 1991;Gorsline et al 1992;D'Alesandro et al 2001;Onuki et al 2003] and in vitro [Zorin et al 1999;Pongjanyajul et al 2000] and data on animals [Shah et al 1981;Matsushima et al 1995] Nicotine system effects, cerebrovascular disease with prolonged exposure, and developmental effects, including pregnancy loss in rats. Therefore, on the basis of the data for this assessment, nicotine is assigned the SK: SYS notation.…”