Intravenous nicotine retards transdermal absorption of nicotine: evidence of blood flow--limited percutaneous absorption.
For most drugs delivered by the transdermal route, percutaneous absorption is limited by the rate of release of the drug from the device or by diffusion across the stratum corneum. However, systemic absorption also requires that the drug be taken up by dermal blood vessels. As part of a bioavailability study of a transdermal delivery system, we observed that a concomitant intravenous infusion of nicotine had a marked effect on the absorption kinetics of transdermal nicotine. Plasma concentrations of nicotine rose less rapidly, reached a lower peak, and peaked at a later time, indicating delayed absorption of transdermal nicotine after intravenous nicotine versus after transdermal nicotine administered alone. Nicotine is known to produce cutaneous vasoconstriction. The likely explanation for our observation is that intravenous nicotine constricts dermal blood vessels, thereby limiting percutaneous absorption. Other vasoconstrictor drugs would be expected to retard the absorption of transdermal nicotine and perhaps other transdermal drugs as well.
Benowitz
N L
NL
Clinical Pharmacology Unit of the Medical Service, San Francisco General Hospital Medical Center, University of California.
Jacob
P
P
Olsson
P
P
Johansson
C J
CJ
D000279:Administration, Cutaneous; D000328:Adult; D001682:Biological Availability; D001783:Blood Flow Velocity / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D003692:Delayed-Action Preparations; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D012867:Skin / Q000098:blood supply; D012869:Skin Absorption / Q000187:drug effects*
D003692:Delayed-Action Preparations; D009538:Nicotine