ABSTRACT
To evaluate potential adverse effects from inadvertent exposure to a nicotine transdermal system or "patch", three marketed products were administered topically and orally to dogs: Nicoderm (nicotine transdermal system), with a drug reservoir and a rate-controlling membrane; Nicotinell, with a nicotine solution dispersed in a cotton gauze pad between layers of adhesive; and Niconil, with a nicotine gel matrix. Nicotine doses during topical administration ranged from 1 to 2 mg/kg/24 h for all three products, with plasma nicotine concentrations as high as 43 ng/mL. Two of the 12 topical exposures (with Nicotinell and Niconil) were associated with clinical signs (excess salivation or emesis). The oral doses from the products ranged from 2.8 mg/kg (one patch) to 13.4 mg/kg (two patches) over 25-57 h, with mean maximal plasma levels of 73 ng/mL for two patches (mean maximal level 36 ng/mL). These doses are 2-9-fold higher than oral doses reported to produce severe toxicity in children and, at the highest dose, within the known lethal range for dogs. Oral dosing of Nicotinell and Niconil (two patches per dog) produced vomiting in 2 of 12 exposures. No clinical signs were observed with either topical or oral dosing of Nicodem. These data suggest that nicotine toxicity in dogs from nicotine transdermal patches may not be as severe as might be anticipated based on nicotine content alone.
Subject(s)
Nicotine/adverse effects , Nicotine/pharmacokinetics , Administration, Oral , Administration, Topical , Animals , Chemistry, Pharmaceutical , Dogs , Female , Nicotine/analogs & derivatives , Skin Absorption , Time FactorsABSTRACT
Several bioactive peptides were isolated from some annelids. Each of the annelidan peptides seemed to be a member of a previously found molluscan peptide family.