Pharmacokinetics of a 16-Hour Transdermal Nicotine Patch

Abstract

A nicotine transdermal delivery system (NTDS) designed to deliver 15 mg/16 hours (Nicotrol®) was applied to 40 healthy smoking volunteers in 3 separate studies: A single administration to different body sites, a multiple-dose study with 16-hour repeated application for 6 days, and a single-dose study with a 16-hour versus a 24-hour application period. The resulting plasma nicotine concentration profiles were similar after application to the arm or the hip with maximum nicotine concentrations of approximately 13 µg/L attained after 8 to 10 hours. The nicotine half-life after removal of the patch was approximately 4 hours. When applying the NTDS daily for a 16-hour period, nicotine stored in a shallow skin compartment was emptied during the nonapplication night-time period, and the repeat-dose study over 6 days showed no accumulation of plasma nicotine. Compared with an average nicotine intake of 15 mg/16 hours when applying NTDS according to recommendation, wearing it for 24 hours resulted in an additional nicotine release of only 2 to 3mg. This profile of nicotine release lends support to the idea of Nicotrol® being a daytime (16-hour) delivery system. Pharmacokinetic simulation indicated that the transdermal system itself determines the flux so an increase in cutaneous blood flow would have no major influence on the nicotine plasma concentration-time profile.