Pharmacokinetics and bioavailability of nicotine in healthy volunteers following single and repeated administration of different doses of transdermal nicotine systems.
Healthy nicotine-dependent smokers were applied different doses of transdermal nicotine systems (TNS) during single and repeated administrations. Plasma and urine nicotine and cotinine concentrations were determined by high performance liquid chromatography (HPLC). After single application of TNS, the maximal concentration (Cmax) and area under curve (AUC) of nicotine in plasma as well as the amount of nicotine excreted in urine were linearly related to the dose. The stable urinary cotinine excretion was not influenced by the amount of nicotine delivered by the TNS. The relevant 24 h plasma nicotine concentration reached after TNS application compares well with the plasma nicotine footpoints--not the peaks--observed in moderate to heavy cigarette smokers. A comparison between different nicotine doses from different TNS allowed to conclude to the functionality of the systems as regards pharmacokinetics and bioavailability. One or two hours after removal of the systems, there was a very slow decline of the nicotine concentrations. After repeated application of TNS, there was evidence for only a very limited nicotine accumulation in plasma (+14%) or in urine (+9%) over 10 days. The steady-state of nicotine was reached within 4 days. The continuous delivery of nicotine over 24 h resulted in an early morning plasma concentration which probably decreases or prevents the craving for the first cigarette.
Dubois
J P
JP
Pharmaceutical Division, Ciba-Geigy, Ltd., Basle, Switzerland.
Sioufi
A
A
Müller
P
P
Mauli
D
D
Imhof
P R
PR
D000279:Administration, Cutaneous; D001682:Biological Availability; D003367:Cotinine / Q000097:blood / Q000652:urine; D006801:Humans; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012907:Smoking / Q000378:metabolism
D009538:Nicotine; D003367:Cotinine