A noninvasive method for delivering controlled doses of nicotine via cigarette smoke

Abstract

A cigarette-smoke delivery system is described in which nicotine dosage was delimited by having the subject inhale a measured amount of smoke to a predetermined depth and duration of inhalation. A plastic syringe was used to "inject" a specified amount of cigarette smoke into the subject's mouth, and an airbag containing 1 liter of air was used to provide a "chaser" with a fixed volume of inhalation for the smoke. Using plasma nicotine boost as an indicator, dose control was found to be nearly linear for the three dose levels employed; in the high-dose condition, plasma nicotine levels were moderately consistent within subjects over three successive administrations. Between-subject variability was considerably greater than within-subject variability, however, suggesting that each smoker obtained a characteristic nicotine boost that reflected individual differences in nicotine pharmacokinetics in addition to nicotine intake per se.

Controlled dosing of nicotine via anIntranasalNicotineAerosolDeliveryDevice (INADD)

“…This is consistent with previous observations of individual variability in nicotine pharmacokinetics (Benowitz et al 1982;Feyerabend et al 1985;Pomerleau et al 1989b). Specifically, Benowitz (1991) has noted that even in the case of intravenous nicotine administration (where bioavailability is fully controlled), there can be up to fourfold differences in nicotine metabolism in smokers.…”

“…Specifically, Benowitz (1991) has noted that even in the case of intravenous nicotine administration (where bioavailability is fully controlled), there can be up to fourfold differences in nicotine metabolism in smokers. While the level of variability for the present aerosol dosing method is somewhat greater than was found for intravenous nicotine administration procedures (see review by Pomerleau et al 1989b), the difference does not necessarily reflect deficient dose control. A possible explanation is that rapid administration of nicotine increases the potential for between-subject variation in the rate of distribution, thus exaggerating variability in plasma nicotine levels measured shortly after dosing.…”

“…At the other extreme, the control of dosing by delimiting smoke inhalation (e.g., pre-determining the parameters of puffing topography) is safe on an acute basis and has enjoyed some degree of success (Zacny and Stitzer 1986;Gilbert et al 1989;Pomerleau et al 1989b;Cherek et al 1991); furthermore, such techniques are highly acceptable to smokers, and the dosing kinetics are equivalent to ordinary smoking. Unfortunately, the approach does not lend itself to the study of either never-smokers or exsmokers-groups whose investigation may shed light on the nature of nicotine reinforcement or the persistence of adaptation to nicotine.…”

Controlling puff volume without disrupting smoking topography

“…The use of an airbag or spirometer (Rose et al, 1985;Pomerleau et al, 1989) would make it possible to combine puff volume control with inhalation volume control. However, Gilbert et al (1988) have recently shown that the experimenter can ensure quantitative nicotine delivery simply by instructing subjects to inhale each puff deeply, with the mouth open, and verifying inhalation by watching for any smoke leaking from the subject's mouth.…”

“…Variations of this method (e.g., smokeis injected from a syringe directly intothe subject's mouth) havebeenbeen tested and found to yield control over nicotine delivery (Gilbert, Jensen, & Meliska, 1988;Pomerleau, Rose, Pomerleau,& Majchrzak, 1989).However,the problem remains of artificiality introduced by the absence of draw resistance. Also, these methods are not suitablefor aerosols consisting of large particles.…”