Pharmacokinetics of nicotine in healthy elderly people.

Abstract

Mortality hazards of smoking extend well into later life; this suggests that smoking cessation will continue to improve life expectancy in older people. The pharmacology and pharmacokinetics of nicotine have not been studied in elderly subjects. Drug disposition and pharmacodynamic responsiveness to nicotine may change with age, and conclusions founded on data from studies of younger populations may not apply to elderly populations. Our aim was to assess the pharmacokinetics of nicotine in healthy elderly subjects compared with healthy adults. Twenty healthy elderly subjects (age, 65-76 years) and 20 healthy adult subjects (age, 22-43 years) were given an intravenous infusion of 0.028 mg/kg of nicotine over 10 minutes. Nicotine and cotinine concentrations were measured in plasma and urine. Heart rate and blood pressure were monitored. For most adult and elderly subjects nicotine distributed according to a two-compartment system. Even though there was a large interindividual variation within and overlap between groups, nicotine total clearance (-23%), nonrenal clearance (-21%), renal clearance (-49%), volume of central compartment (-37%), volume of distribution at steady state (-17%), and cotinine renal clearance (-18%) were statistically significantly decreased in elderly subjects compared with adults. Maximal heart rate response to nicotine was decreased in the elderly subjects (-29%). Even though statistically significant differences were observed, the disposition of nicotine does not seem to be changed to a clinically important extent in elderly subjects compared with younger adults.