Pharmacokinetics of Nicotine ebooksclub.org Tobacco or Health Physiological and Social Damages Caused by Tobacco Smoking Second Edition
Cigarettes
Snuff
Chewing tobacco Chewing gum
20 15
10 5
15 10
5 −10 0
30 60
90 120
−10 0 30
60 90
120
Minutes Nicotine Plasma Level [ngml]
15 10
5
15 10
5
Fig. 4.5
Changesinplasmanicotinelevelsinresponsetocigarettes,snufftobacco,chewingtobacco andnicotinechewinggumsingledose
[52,55] .Consumptionofonecigarette12puffsover9
min,2.5gtobaccokeptinthemouthfor30min,8gchewingtobaccochewedfor30minand 4mgchewinggumchewedfor30min
1 3
5 7
9 11
20 40
Nicotine Plasma Le vel [ngml] 60
80 P1
P2 P3
P1 P2
P3 100
arterial level
venous level Controls
Time [min] after smoking of a cigarette
Fig. 4.6
Arterialandvenous plasmalevelsofnicotine
followinginhalationofone cigarette.Dataforthree
smokers;opensymbols: arterial,solidsymbols:venous
plasmalevelsofnicotine [56]
50 40
30 20
10
12 10
8 6
4 2
8 12
16 20
24 4
8 [h] n = 10
Nicotine [ngml blood]
co-Hb n = 7
Fig. 4.7
Meannicotine plasmalevelsand
CO-haemoglobinlevelsin cigarettesmokers.The
subjectssmokedone cigaretteoflowdotted
linesandhighnicotine contentsolidlineevery
30minfrom08:30to23:00 atotalof30cigarettesday.
Thecigarettesinquestion wereproducedforresearch
purposes [57]
N Nicotine
Nicotin-iminium Aldehyde
oxidase
Cotinine 5-Hydroxy-nicotine
Urinary excretion
Nicotine-N-oxide Flavoenzyme
N N
N N
N N
N H
H OH
H
H H
P450
N N
CH
3
CH
3
CH
3
CH
3
CH
3
O O
Fig. 4.8
Metabolismofnicotineschematicillustration
accumulatesandiseliminatedmuchmoreslowlyhalf-life20–30h,withtheresultthat itcanbeusedforassaypurposesinsmokersandpassivesmokers
[59] .Quantitativemeth-
odse.g.gaschromatographymassspectrometryorGCMSformeasuringurinecotinine, whichhasalongerhalf-life,arevalidandreliable,thoughcostlyandtime-consuming.
Recentlydevelopedsemi-quantitativeurinecotininemeasurementtechniquesi.e.urine immunoassayteststripsorITSaddressthesedisadvantages,thoughthevalueofITSas
ameansofidentifyingabstainingsmokershasnotbeenevaluated.Therefore,Acostaetal. examinedITSasameasureofsmokingstatusintemporarilyabstainingsmokers
[60] .
Atotalof236breathandurinesampleswerecollectedfromsmokerswhoparticipatedin two separate studies involving three independent, 96-h i.e. Monday–Friday, Latin-
square-ordered,abstinenceorsmokingconditions;aminimum72-hwashoutseparated eachcondition.EachurinesamplewasanalysedwithGCMSandITS.Underthesestudy
conditions,COdemonstratedmoderatesensitivity83.1andstrongspeciicity100, whereasITSassessmentshowedstrongsensitivity98.5andweakspeciicity58.5.
Inthisstudyofshort-termabstinence,ITSclassiiedasnon-abstinentnearlyhalfofthe samplescollectedfromabstainingsmokers.However,itclassiiednearlyallnon-absti-
nentsmokersascurrentlysmoking.TheresearchesconcludedthatthevalidationofITS usingGCMSresultsfromsmokersundergoingmorethan96hofabstinencemaybe
valuable [60]
. NicotineN-oxideisnotofpharmacologicalinterest
[58] .Theextensivehepaticmetab-
olismofnicotinemaymeanthateliminationisdelayedwhereliverfunctionisclearly impaired; the administration of nicotine should, therefore, be assessed with caution in
individualswithverymarkedimpairmentofhepaticandrenalfunction. Thespecialistliteraturecontainsaccuratedescriptionsofthepharmacokineticproperties
ofnicotinefromcigarettes,oneparticularfeaturebeingthatitsextremelyrapiddeliverytothe CNSisnotachievedbyanyproductusedfornicotinereplacementtherapyFigs.
4.5 ,
4.9 and
Figs. 11.1
– 11.3
in Chap.11
[62,63]
.Theamountofnicotineabsorbeddailyasaresultof cigarettesmokingdependsonthenumberofcigarettessmoked,theirnicotineyield,thenum-
berofpuffstakenandthedepthtowhichthesmokeisinhaled.Withinafewhours,a“depen- dentsmoker”canattainplasmanicotinelevelsthatareperceivedassuficientforawhole
day.Thebodyabsorbsnicotinemoreslowlyfromnicotinepreparationsinhalersnasal spraychewinggumpatchthanfromcigarettesmokingFig.
4.9 .Theseproductsnever
achievethepeaknicotinelevelsattainedbysmoking,althoughconsiderableinter-individual differencesexist.
5 2
4 6
8 10
12 14
10 15
20 25
Minutes Increase in nicotine
concentration ngmL
30
Cigarette Gum 4 mg
Gum 2 mg Inhaler
Nasal Spray Patch
Fig. 4.9
Comparisonof plasmanicotinelevels
followinginhalationofone cigarettewithlevels
followingnasalspray 1mg,inhaler1mgand
chewinggum2mg [61]
Forthemostpart,pharmacokineticstudieswithnicotinepreparationstakeaccountof plasmanicotinelevelsovertime,whereasinclinicalstudies,plasmacotinineorthiocyanate
levelsalsoyieldimportantinformation.