PLASMA-LEVELS OF NICOTINE AND SAFETY OF SMOKERS WEARING TRANSDERMAL DELIVERY SYSTEMS DURING MULTIPLE SIMULTANEOUS INTAKE OF NICOTINE AND DURING EXERCISE

Although transdermal nicotine patches have been studied extensively un der recommended conditions, the present studies were designed to asses s the nicotine plasma levels and she safety of transdermal nicotine pa tches in smokers undergoing situations suspected to result in increase d nicotine plasma levels. The first study examined the effects of incr easing nicotine intake through sequential administration of a nicotine patch (day 2), a patch followed by consumption of nicotine gum (day 3 ), and a patch followed by gum consumption and cigarette smoking (day 4). In this study, nicotine plasma levels increased transiently after the addition of each nicotine sour ce. Mean areas under the concentrat ion-time curves from 0 to 24 hours (AUC(0-24)) for nicotine were 453 /- 120 ng.hr/mL (day 2), 489 +/- 143 ng.hr/mL (day 3), and 485 +/- 143 ng.hr/mL (day 4). The second study evaluated the effects of physical exercise on the kinetics and the safety of two different types of nico tine transdermal devices: Nicoderm and Habitrol. The mean delivered do se of nicotine was higher with Nicoderm compared with Habitrol, and th e two products were not considered to be bioequivalent. During a 20-mi nute exercise period, nicotine plasma levels increased by 13 +/- 9% fo r Nicoderm and 30 +/- 20% for Habitrol. This increase in nicotine plas ma levels was probably related to the exercise-induced increase in per ipheral circulation or the patch site. Results from both studies indic ate a clinically nonsignificant increase in blood pressure and heart r ate after the administration of nicotine. After exercise, subjects tak ing Habitrol tended to have a higher incidence of adverse events compa red with baseline values. Safety profiles remained acceptable in both studies despite the increases in nicotine plasma levels. It was conclu ded that both superimposed nicotine sources and physical exertion resu lt in short-lived plasma nicotine elevations and temporarily increase nicotine pharmacodynamic parameters without increased risk to the volu nteers.