title: Time controlled pulsatile transdermal delivery of nicotine: A phase I feasibility trial in male smokers.
abstract: Nicotine substitution is a mainstay component in smoking cessation schemes. Current products including patches are poorly effective mainly because they do not give smokers the same pharmacokinetic profile of nicotine as cigarette consumption. This work evaluates a new computer operated delivery system for time controlled pulsatile transdermal administration of nicotine in a phase I clinical trial with twelve heavy smoking male volunteers. The device was affixed to the ventral side of the leading lower arm of the subjects and was programmed to deliver two pulses of drug within 16h with three delivery rates in a consecutive dose escalation study. Tolerability of the three increasing doses of nicotine was established. Plasma concentration of nicotine exhibited two peaks and one trough and reached therapeutically effective levels that behaved linearly with the drug load concentration of the device. In vivo input rate, delivered amount and elimination kinetics were deduced by pharmacokinetic modeling to analyze device performance. Timing, dose and duration of delivery were controlled by system operation parameters. Hence, feasibility of controlled pulsatile delivery of nicotine at predetermined intervals was demonstrated. After additional optimization, preprogrammed or on demand administration to meet individualized and circadian replacement needs should improve smoking cessation efficacy.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Basel, University of Basel, Petersgraben 4, 4031 Basel, Switzerland.
authors.forename: Felix
authors.initials: F
authors.lastname: Hammann
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Basel, University of Basel, Petersgraben 4, 4031 Basel, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kummer
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Basel, University of Basel, Petersgraben 4, 4031 Basel, Switzerland.
authors.forename: Stefania
authors.initials: S
authors.lastname: Guercioni
authors.affiliation: School of Life Sciences, Institute of Pharma Technology, University of Applied Sciences Northwestern Switzerland, Gründenstrasse 40, 4132 Muttenz/Basel, Switzerland; Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland. Electronic address: georgios.imanidis@unibas.ch.
authors.forename: Georgios
authors.initials: G
authors.lastname: Imanidis
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Basel, University of Basel, Petersgraben 4, 4031 Basel, Switzerland.
authors.forename: Juergen
authors.initials: J
authors.lastname: Drewe
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000074285:Smokers; D055815:Young Adult
chemical_list: D009538:Nicotine
keywords: Clinical trial; Controlled pulsatile delivery; Nicotine; Pharmacokinetics; Programmable device; Transdermal drug delivery