Animal model and pharmacokinetic interpretation of nicotine poisoning in man.
The purpose of the study was to find an animal model and possible pharmacolokinetic interpretation of  the fact that a patient survived an accidental sc poisoning with a nicotine-containing animal tranquilizing dart. The same dose size of 3.58 mg/kg causing poisoning in man was administered to rabbits iv and sc. Blood samples were obtained for nicotine analysis by cardiac punctures; and blood pressure, respiration rate, and saliva flow were measured. Analysis of the original solution used in the dart excluded the possibility of sub-potency. The extent of unchanged drug reaching systemic circulation (extent of bioavailability) upon sc administration was 83%. Hence, the possibility  of survival in man due to rapid tissue metabolism was ruled out. The pharmacokinetic analysis revealed a significant reduction in sc plasma levels during the first half hour which is reported as the most critical period for patients experiencing nicotine intoxication. The disposition of nicotine in the rabbit, i.e. distribution and elimination, are identical upon iv and sc administration. The reduced toxicity, i.e. blood pressure and saliva flow rate, upon sc dosing may be explained by the difference in plasma level peaks between sc and iv administration.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D007700:Kinetics; D008297:Male; D009538:Nicotine / Q000378:metabolism / Q000506:poisoning*; D011817:Rabbits; D012119:Respiration / Q000187:drug effects; D012472:Salivation / Q000187:drug effects; D013997:Time Factors
D009538:Nicotine