RESMARCE & nVIELCPHE!r.
Re. : Transdar=il '14-cctiae
1. 3ackgr--rand
Since tits =--;d-7,O's phar=accl.-gical support in breaking the
smoking hattt !:y 71474ng dozes -if has been under
discussion ird has led to the launch" of @.-wo types of
product. L-e-o,
Chewing 7= ccntatnizq Micot-:r
(in Gar=I.?XY` rricoretzi.,, Boehringer manahs-4=)
2. Nicot-;-%e plasters
(Ir. G;r=ai%y !ricot.4nell =S, Ciba G*igy; 'Nikofranor.,
Refa-Franon Arzneimittal GmbF.)
Other types of plaster are being clInically tested or have
already been registered worldwide (e.g. Nicolan, Elan;
sold in USA by Warner-Lambert).
n their pharmacological effects both forms of application
V/'Idiffer quize, clearly from nicotine i--zake via smoking.
Nicotine intake is slow and continuous - with chewing gum
containing nicotine over a period of approx. 20-30 minutes
after which intake slowly ceases (1) - with plaster ever a
period of 4-7 hours until a plateau is reached (2). The
nicotine concentrations measured in the blood fluctuate
interindividually and are somewhat lower than those found
among smokers (3,4).
in contrast to this. smoking induces very rapid nicotine
intake which Means that maximum concentrations in the
blood are achieved within 10 minutes and then subside
again quickly M.
VI'
The slow increase in nicotine concentration and the longer
period during which it remains high mean that the- nicotine
receptors 4n the central nervous system adapt/are blocked:
this in tur= -loans that the stimulating effects achieved
by s--oking cannot be achieved with these products (5) .
On the other hand, -he al=asc constantly high nicotine
level sup;rasses wit.h.drawal Symptons.
Z-1
11. Compartson of chewing got. plaster (5,S) C)
C:I
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,I) GU= Q4
C)
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Gradual increase and decrease -9n n-;cot';ne concentration
during the day; during the night tie nicotine level
subsides. As It is discontinuous.' the nicotine remains
effective fror. day to day.
b) Plaster
Gradual incraase and !or=at-4on of a plateau which
:1 -
remains almost constant. The mi co cine level does not
subside overnight (24-hour plaster).
2. Advantages:
a) Guz
The smoker can organize intake :o suit himself. I%ctivt
control -over intake and the condition it produces.
b) Plaster
Simple form o! application. independent of any
situation, and invisible.
3. Disadvantages:
a) GU--
Problems fit!% flavour and chewing. In some cases nausea
and headaches. The danger of addiction.
b) Plaster
In some cases skin irritation. in isolated cases nausea
and sweating. Theoretically the danger of total
nicotine intolerance.
111. Therapeutical effect:
The effect of therapies to break the smoking habit using
plasters or chewing gum is disputed. In the short term (a
few weeks) far higher abstinence rates are observed. After
1-2 years. however, these have adapted themselves to the
rates of placebo or control groups which means that most
investigations do not establish success rates which are
signif icantly better..
For this reason an Rdditional behaviour therapy is
recommended in almost all applications (2,7,9,9).
IV. STOWIC - Product:
The produce. is a plaster which is manufactured using an
innovative combination release membrane/matrix for the
active substance.
Compared with other products this is intanded to achieve a
more even release rate for the acri7e substance which is
less dependen,: an its 4-nit.4-al concentration (Pat. WO
89/07959).
:ks the example %,ut the pr---c--;Ie ;-a said
t: i-le ap;1-4cab:e zo cthsr ictive subs=3ncas, too.
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As rho ;rtnctple of nicotine application does not differ
from that of other ;roducts (Enc. 1)7the pharzacoloq'ical
effect of the product ,with all its advantages and
disadvantages is equivalent to that of the other nicotine
substitute products.
The somewhat faster tbsor;tior. of nicotine which Stowic
emphasizes and thus the =ore rapid achievement of a
plateau should not be seen as a product advantage compared
with smoking because of the generally differing pharmacc-
dyna=ics.
Use over a period *f only 16 hours is also racloz-mended for
t!%e products of tho- cc,.,.pat4.tors (e.g. Rabi I'll I
'rho impr2ved der=ato-logical sensizivity and lower
production costs cannot be conclusively appraised with the
currently available infor--ation.
Nicotine application it the treatment of Alzheimer's and
Parkinson's disease is under discussion worldwide and is
being clinically tested in some cases (10)
As far a; is known today, success is only possible if the
development of nicotine intolerance is avoided.
Accordingly, Nicotine has to be applied short-term in
small dozes (e.g.' inhalation, nasal sprays) (11) .
TUC Cn
L The transde=al application of other pharmaceutical
products is documented i; several patents and is the
object of numerous research projects being carried out by
the pharmaceutical industry.
V. Alternatives:
The rapid, peaking intake of nicotine which the smoker
V, clearly wants cannot be achieved with nicotine application
via chewing gum or plaster (Enc. 2).
To overcome this disadvantage other forms of nicotine
intake are necessary.-
For this reason intensive work is being carried out an
developing nasal sprays and inhalators (Favor type). Some
are already undergoing clinical tests (6).
The disadvantage of rapid nicotine intake similar to that
achieved with a cigarette is seen in the danger of people
possibly becc=inq dependent on it.
Successes in breaking Vle smoking habit are therefore seen
Za a cambinat'on of slow and fast-working nicotine release
s7stems tailored to Individual needs.
Enc. 3 (fr@zm 6) provides an overview of nicotine
substituto systems t4hich are already available or are
'hoing tested.
NJ
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V1.Literazure:
1.BEITOWIn- IT.L., Now Erql. J. Had. 319. 1318 (1988)
2.ROSE JR.E.. in Tho Clinical Management of Nicotine
Dependauce, ad. J.A. Cocores 196, S;r4-nqer publishing
house (1991)
3.DUBOA'S J.?. eta!., Meth. Find. Exp. Clinic. Phar=acol.
11, 197 (1989)
4.BEHOWITZ N.L. otal., Clinic. Pharzacol. Thor. 41, 467
(1987)
S.BvV.OWTTZ H.L.. Brit. J. Addict. SS. 495 (1991)
6.RUSSEL M.X.H.. Brit. T. Addict. 86. 653 (1991)
7.ZVKCS In. eta!.. Chest 1-00(2(S)), 4S (1991)
S.F.MT R.D.R., Mayo Clinic. Proc. 65, 1529 (1990)
9.GOLZSTEIT; M.G., NTAVRA R., in The Clinical Management
of tflcctine Dependence, ed. J.A. Coccres 181, Springer
publishing house (1991)
10.NEWHOUSE P.A., HUGHES J.R., Brit. j. Iddict. 86, 521
(199i)
11. ADLKCF=-R personal information
Ln
BATCo document for Province of BritiSh Columbia 23 April 1999