Abstract
The plasma concentration–time profiles and pharmacokinetics were characterized for nicotine and its major metabolite, cotinine, after multiple daily application of a nicotine user-activated transdermal therapeutic system (UATTS) to nine healthy smokers. The volunteers abstained from smoking 24 hr prior to and during the course of the study. A 10-cm2 system (designed to deliver 75 µg/cm2/hr) was applied every 24 hr for 5 days, with serial blood samples taken on Days 1 and 5 and after system removal on Day 5. Generally, the nicotine UATTS was well tolerated. Predose nicotine concentrations on Days 3 to 5 indicated that steady state was reached by Day 3. The nicotine pharmacokinetic parameters for Day 1 and Day 5 were similar: the mean (SD) AUC(0-24) values for Days 1 and 5 were 271.7 (50.7) and 311.7 (55.0) ng · hr/ml, the mean (SD) C max values were 16.3 (2.6) and 16.8 (2.9) ng/ml, and the median (range) T max values on Days 1 and 5 were 12 (9–24) hr and 12 (0–24) hr, respectively. There was only slight or no accumulation of nicotine after multiple dosing as indicated by the Day 5 to Day 1 AUC and C max ratios of 1.15 (0.09) and 0.98 (0.06), respectively. Overall, the UATTS system maintained relatively constant plasma nicotine concentrations and is suitable for once-daily application.
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Ross, H.D., Chan, K.K.H., Piraino, A.J. et al. Pharmacokinetics of Multiple Daily Transdermal Doses of Nicotine in Healthy Smokers. Pharm Res 8, 385–388 (1991). https://doi.org/10.1023/A:1015810019076
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DOI: https://doi.org/10.1023/A:1015810019076