Pharmacokinetics of multiple daily transdermal doses of nicotine in healthy smokers.
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 micrograms/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) Cmax values were 16.3 (2.6) and 16.8 (2.9) ng/ml, and the median (range) Tmax 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 Cmax 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.
Ross
H D
HD
Drug Development Department, CIBA-GEIGY Corporation, Ardsley, New York 10502.
Chan
K K
KK
Piraino
A J
AJ
John
V A
VA
D000279:Administration, Cutaneous; D000328:Adult; D003367:Cotinine / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D012907:Smoking / Q000378:metabolism*
D009538:Nicotine; D003367:Cotinine