Stable isotope method for studying transdermal drug absorption: the nicotine patch.
A stable isotope-labeled drug method was used to determine the absolute bioavailability and absorption kinetics of a transdermal nicotine-delivery system (TTS). TTSs are being developed as an adjunct to smoking-cessation therapy. Deuterium-labeled nicotine was infused for 24 hours simultaneously to TTS application in cigarette-abstinent smokers. In 11 subjects with good patch adhesion, an average systemic dose of 19 mg nicotine was delivered, with average absolute bioavailability of 82%. The rate of nicotine absorption was maximal between 6 and 12 hours after TTS application and declined thereafter, plateauing between 16 and 24 hours at 62% of the maximal rate. Ten percent of nicotine was absorbed after the TTS was removed, demonstrating a reservoir for nicotine in the skin. Our study demonstrates the applicability of stable isotope methods in understanding the clinical pharmacology of transdermal drugs.
Benowitz
N L
NL
Clinical Pharmacology Unit of the Medical Service, San Francisco General Hospital Medical Center, CA 94110.
Chan
K
K
Denaro
C P
CP
Jacob
P
P
D000279:Administration, Cutaneous; D000328:Adult; D001682:Biological Availability; D003903:Deuterium; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012869:Skin Absorption; D012907:Smoking / Q000009:adverse effects*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism*
D009538:Nicotine; D003903:Deuterium