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.
Clinical Pharmacology Unit of the Medical Service, San Francisco General Hospital Medical Center, CA 94110.
N L
NL
Benowitz
K
K
Chan
C P
CP
Denaro
P
P
Jacob
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