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Altered disposition of repeated nicotine doses in rats
immunized against nicotine.
Keyler DE, Hieda Y, St Peter J, Pentel PR.
College of Pharmacy, University of Minnesota, Minneapolis, USA.
Active immunization of rats against nicotine reduces the distribution of a
single intravenous dose of nicotine to brain. The current study examined the
effects of immunization on the distribution of repeated doses of nicotine,
and on estimates of nicotine pharmacokinetic parameters. Groups of rats
received five repeated doses of nicotine over 80 min (total dose equivalent
to the nicotine intake from one, three or 10 cigarettes in a human). The
serum nicotine concentration in immunized rats was 160-430% higher than
controls after the fifth dose, demonstrating binding of nicotine to
antibody. Brain nicotine concentration in immunized rats was reduced by
30-46%. The reduction in distribution of nicotine to brain correlated with
the serum hapten-specific antibody concentration, the percentage of nicotine
bound in serum, and with the unbound nicotine concentration in serum. In
immunized rats, nicotine had a smaller steady state volume of distribution,
lower systemic clearance, and longer terminal half-life than in controls.
These data demonstrate that immunization against nicotine reduces nicotine
distribution to brain, even after multiple nicotine doses at rates
approximating heavy cigarette smoking. Whether this reduction in nicotine
distribution is large enough to alter nicotine's physiological or behavioral
effects remains to be studied.
PMID: 11072421 [PubMed - indexed for MEDLINE]
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