Product Design
FTC Yield and Nicotine Uptake in Smokers
Abstract
Reports the relationship between nicotine yields and nicotine uptake in four groups of smokers. Defines these groups as: 1 mg 'tar', ultra-low 'tar' [ULT], full flavor low 'tar' [FFLT] and full flavor [FF] smokers. States subjects smoked their usual brands and submitted urine samples for measuring urinary metabotiles and nicotine. Reports lower yield cigarette smoker's nicotine uptake per day and nicotine per cigarette are lower and states "These data suggest that nicotine uptake is a function of individual smoking behavior within specified "tar" categories." Indicates FTC yield can be used as a predictor of "nicotine uptake by smokers who select cigarettes with a particular FTC "tar" yield."
User-Contributed Notes
Fields
- Author
- Byrd, G.
- *Caldwell, Bill (use Caldwell, William S.) (RJR Biological Chemistry Section Head, Master Scientist)Did SS and ETS Nitrosamine Analyses, c.1988-94
- DeBethizy, Joseph Donald, Ph.D. (RJR toxicologist and director of R&D, c. 1994)
- Robinson, John Howard, Ph.D. (RJR research scientist & psychologist, c. 1994)
- Hypothesis
- FTC machine testing and ratingsDesign changes to achieve altered FTC smoke machine tar and nicotine ratings, with or without measured changes in human intake.
- Inhalation ProfileAre cigarettes designed to cater to individual inhalation profiles?
- Low-yield cigarettesModification of low yield products to assure that adequate levels of nicotine delivery are maintained, and effects of yield changes on toxicity and dependence.
- Mainstream constituent yieldsModification of selected mainstream smoke constituents in response to health concerns.
- Measuring human intakeDevelopment of scientifically valid procedures for measuring tar and nicotine levels that more accurately reflect human intake.
- Nicotine transport, transfer, and uptakeDesign changes which alter nicotine delivery or effect how the product causes and maintains dependence, including transfer of nicotine from tobacco to smoke, and uptake into the body.
- Smoke constituent testingDevelopment of methods for measurement of gas and particulate yields in mainstream and sidestream smoke.
- Smoking psychology and behavior
- Keyword
- Blood nicotine
- Intake (Smoker yield)
- Low delivery (Reduced delivery)
- Metabolite
- Nicotine delivery (Smoke nicotine or nicotine yield)
- Self-administration
- Tar/Nicotine ratio (Nicotine/Tar Ratio or T/N ratio)
- Total particulate matter (TPM or Tar)
- Smoke Constituent
- Nicotine
- Total particulate matter
- Named Organization
- Coresta (Industry-affiliated Int'l scientific/research group)An international organization whose objective is "to improve cooperation in scientific research and tobacco." Consists of 186 member companies/institute from 54 countries, including tobacco, paper and filter companies, and universities engaged in tobacco research.
- Federal Trade Commission (Enforcement agency for laws against deceptive advertising)Enforces laws against false and deceptive advertising, including ads for tobacco products. Ensures proper display of health warnings in ads and on tobacco products;collects and reports to Congress information concerning cigarette and smokeless tobacco advertising, sales expenditures, and the tar, nicotine, and carbon monoxide content of cigarettes.
- R.J. Reynolds Tobacco Co. (Cigarette manufacturer (Camel, Winston, Doral))Cigarette manufacturer (Camel, Winston, Doral)
- Subject
- Blends (Design)
- Filters (Design)
- Low Yield Cigarettes (Products)
- Metabolites (Measures)
- nicotine technology
- Smoke Delivery/Transport (Measures)
- Smoke Nicotine (Measures)
- @smoke_constituents_measures
- T/N Ratios (Measures)
- Tar (Measures)
- Test/Smoke Condensate (Testing)
- Test/Smoke Constituents (Testing)
- Transfer to Smoke (Measures)
- Ventilation (Design)
Document Images
FTC y~I~.I.D AND NICOTINE UPTAKI~ IN SMOKERS
~. John H, Robinson. Willlaiu S. Caldwetl,
~.nd ] Dot1 deBetlli!~"
Re.~ca¢ch and Development. R. J Reyr.old~ Tobacc~ Cotupany, Winston-Salem, NC 27102
pres~nla~ion Number ST23 at Joint M~ttng of CO|~.ESTA Sm~ke ~a~ Techl~olog'¢ Group~
VienrLa~A~st~ia, Scptemt~c~ 0-t4. ]995
536471604
Advances in a~l~ly~ical rncch~dology h,l~ led to f.c¢ca:~ed under,exuding of ni~o¢ine
melabo]]~lll i~ ~Iun~s such ~h~t tli¢~ti~e uptak~ b> smokers c,~ be d~lermln~d "Fo be~e~
urldcrsland the rel~fi~n~hip betwe,~n FTC nitc~dtle yJel~s ~nd actual nicotine uptake by
ci~ar~tt~ smuk~, we have studied nlcoliac ~ipI~k¢ by 33 ~1~kccs ~hat ~psnn~d ~o~¢ 8~p~
Img "laV OMO), uhr~-I~w "t~" (ULT), full-fl~vor Io~, "1~" (FFLT), and furl flavor ~FF)
cigarette smok¢~s. Th¢.~¢ cigarette categories had m~an FTC n~c~tit'~c yields o[0.14,049,
O.~Tand 1.13 mg?cigarctte, tcs~ective~y. $~b~cc~s~u:okcd~dl~/~,rtheirusual brand of
~igarett,. and subnlJttcd a 24 h urine sample over a period wh~rc fl~C n~Jmber of ~igar~ltes
smoked ':.'~ recorded. Ni~..otin~ ~ptake was determined by nl0l~iloring urinary nicotine ~d i;s
mcl~boli~cs, [n¢l!~ding glu~ro~id~ c~aj~g~te.s D~.ily ~ic~fiac upZ=k~ w~ 9.1 • 7 3 m~; for
~MG, 1~.~ 2 = ICfl mg [t~r ULT, ~1 8 .a. 9,4 m~ fi~r FFLT, ai~d 3"/ I ~- [4.4 mg f~t FF
sm~ke~ ~m ,~. per cigaret|e b~is thi~ equaled ~o 023 t. 0 1 [. O 56 • 0.2~. 0.60 ~ O.tg, ~d
gro*aps it~dicated that lower ~:TC yield ci~r~t~ result ~n mlt Olfiy ~s |~i~otin~ uptake p~r 24
h ~erh~d, bu'~ also per cigaxettc smoked Th~se data sug~esl t~al nigofin~ uptake i~ a functi~,n
of b~ivid~al smokiag b~|l~v~or wj~bin sp~ciS~'d "I.~t" cale~ie$ We ~o~lclu,'le from lll~$e
i~ is ~seful i~l predicting and comparing ~¢lual lu¢oti]~e up~e by smokers who ~el~cl
$3fi47160S
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TILe Federal '['r;~dc Cillnnlis,~[on (FI'C) machinc smoking m~hod, adopted hy the lJ S
~ovctru~l~'nL ill I967 {f], iS based oii measur~nLcnt~ flora a xmokin~ machine fifllo~ving ~ ~vdl.
d~ned ~'¢~r~icil qI" a 3~ /IlL put'k'o~ 2 s duralion ~ry 80 ~ {21 Th~ [~I'¢tence mcthod was
~stablis))ed ~b~ pradllct comparison l.ikc any s~andardizcd rnachin¢ srT;okillg m~thod, th~
FTC method ~tfffer~ fnm~ Ib~ fact Ik~I humans do not ne¢cs,~urdy $mok~ in ib.e same w~y a~
ITl~¢hin~S ~,:lJ h ~q[~di~tiog o~ s~c~ok~ ¢~cpO$%lr~ ~)~d on ~[1~ }:TC mCthl~ m~y b~ LIn[~ ~.
C~ld~
~stinx~le ~br ~:tt indiv]dval sm~k~r. N~It~nc uptake hy srnok¢~ is reportedly i~f~ueacod ~o(
only by p~ofll~t compo~itio~ and d~s;~n, but a)~ by s~}oker-cvn~rol~ed p~znl~tcr~ ~puff~ag
pa:~erns, de~lh of inh~l~fion, m~mbcr ~nd frequency of ci'~r~tes. ¢Ic ) ~nd physiological
factors such ~S p~-{ of muc.o~al me~tbr~tne~ I3, 4~..qubjective factor~ (~uch a~ mo~d) n~a~ a[~o
influetlce smoking behavior ~o that an i~ldividual may s01oke each ci~a~ene dilTeretllly G~V~t~
~.{[ these c~msiIIclation~, it ~s unlikely they ~'~ny ftlach~ne-~se~ ~ttl~3km~ tllct~od c(luld
acc~r~le~y pc'e,'lic¢ nic~t+ue uptake for z p~tlieular ~m~ker a~ a p~t~ic~:gar lime for ~ specific
ci~a]ett~ ]n o~der to p~l~. raltchine+b~ed nicolille il~tzke pr~ictit~n$ in perspective, it wo,ld
be ncce~a~ to measure the ac~lt~ I~ieo~e upt~.ke b:,r a sm~ker and ct~m~are that wLth
prcdict~d machine va[ue.~.
Nicoli~le uptake arid nleta~olisttl ~n ~Ltlman~ ~ it complex: [~rOCe~S that re,limits in
e:~cl¢iit~n ~I" illln~:l~,th~ ~rmt~,bolit~,~ [5. G) Acc+)u~l}n~ for lolal ~icotit)¢ I~ptake in
.~rnakets b~
bee~ dlificldt in the past due to a timked und~St,andit:~ of ni~(~tlne n~abolistn in huma~l~ &nd
lack of co6~plthcn~ve analy%ica~ mtthod~ ~eccnt ad+'anc~ in ~naly~eal meihod~ll~gy and
id~.~i~ti~idic~n of n~w nicotine rn~tabolites have ¢llabled us Io d~t~nlir, e nicotino uptake by
~i~1ohcr~ Ibis p~'cS,.3rtI't+{~'O~ r~vicw~ pt'o~:'~s {Oward dct~rni~i,~ nic¢~lJil¢ t~ptahe ~Lrl,~
mel~bnllsm in .~moker~, ll~d repOl~ a study ¢)f ]:TC yP2Jd and nic.oI]ne uplak~ in smokcr~
~t)f~d_~LKtes~ in_l, Sjl.~rs(~ndln~ Nin~lit/¢ NI~t~lloli~m An ~r.tel~iV¢ reviev~ of nira~tino
mclah~flisll~ ,a';ts dot~o ill |9gl at an imp~rtat/I lime ill thi~ f~dd {.~[ For exal~pie, Ira~-y-
hydr~+xya~tiuil~¢ w~s f'~r~t tei~ortc-d to he a major tlcifiar~ m~tzholit.2 il~ hutllans in the
{ale
] 9~fY-; I 7. gl ].~)T~r I;~]]l, si~'liJ'~¢zl~t qll~ndli¢> Of t'~Jnju~Iit~d J~rnls O~ ~¢nt~n~ and
ils
in~taholi~e~ %vct¢ discovered 19-14] Th~s~.. "llli~sin~" metabt~llte:i n~Ixual~y linliled
gttet~lp,,~ Io
$36471606
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mel~bohle.~ i~l sn~)kcl.~ r,luch ,0rogte~s h~.x been m:~dc in the lasl few years ill identifying and
qu~nl~l".'ul~ ni~'lln~ z~('tabo[ite~, b/ic(>liiIC nlet~lisr~ is no',~ ~.~o~n tO involve ex~er~si'ce
l~base J I~JJ~¢lio~,~li/.aficn changes to the xe~tobl~tic) ~.nd ~!l~e 1~ (cc~r!iuga~,ion I~r tile
x~n~biolic wilh an endogenou~ coflt~O~lnd) r~¢~it~tis f(~cenl lit~raltlre ~ug~sls lhe ~ico|in~
me~bo~ir ~¢benle ~)~ h~lrA~n~ ~own in Fi,~u~¢ I I 15-17]¸ A~thou.gh nol e×haustive in scope,
th~s scheme ~¢cour, ts f~)r all major and s~ver~l i~in~r nicotine met~botites N~cotin¢
metabolism is J~)edi~ed by tiiffcrent enzymes in ~he hod)'. Ti~s mos~ significant rn~boLic
pathway Ib~ r~ic~tine i,~ initiated by ey~oehrom¢ ,0450 catalyzed alpha oxldafio~ producing
nicotJne-I ',5'-il)~ni~m ion, an~ ~o a lesser cxter~t, n~co~ine.~'-ra~ti~ylene h~it~iun~ io~ 116,
1~-
21 ~ l'ormat~t~n of 'nic, otine-I ',2'-izrdni~tm ior. (not ~tlown) has bee~ postulated [22]~
however.
re~enI evide)~ce .~)ggesls il is not p~¢~e)~t in s~okers' urtne [2~ 24j Nic~tlne-l',5"-imirdu~
ion i~ c¢~l~vertu~ by aldehyde oxygcI~e to colini~ [25]¸ Co~inir, e i~ e×ten~iv¢ly melabolized
~ il~ gl~cu~ol~idc ¢cmjug~te. to coti~i~e-N-oxid¢, and presumably t~/r~t~]'~h~droxycotinir, e
though none tff tili~ major urinary metabolite was fot~n~ in h~ll"oaa hepalocyle~ itlctlba~vd with
nlcoti~)e 1261 Nicofi~e-N'-o×ide is produced exc~us~vdy ~ ttie lr~)$ isomer in hugtans by ~.
flavin-cc~nt,d;lmg ~ont~oxygenase (FMO) (16, 25] Nicatin~-N-glucuronid¢ is f~r'med
pres~)n)~b]), ~bn)ugh t})e .~clion of ~ridine diph~)~ph.~e-~l~¢ur~osy]~nsfer~se B~th ~f ~heae
ptod~icts ale excr,:led unchanged and are als¢~ f~rmcd by huma~ hcpato~ytes tt~ virtu It9] A
i}1i1~¢~1 atl)o~lr~l o¢ nitu31~/l~ is conVerlvd 53 iL¢; N-raethy}c~c ir~ittiu~ iun ~o ,0roduce
nornieotir~e
[27] ~r~d ~.:S~ibly norcotinine as show~ The N-glucu~unid~ cc~njugates ,~f nicotCne aJad
c~l~nine have b~,e;~ de~ermined by direct me~ods [13, 14, 28} I1 has been repotted that lrarz~-
3'-hydroxycntln~e ig glucumnidated on the I~yd;~:y[ axygcn ~-~ shown in Figure I [291
'1 be ~rm,~ry di~tnbullon of the r~zjor a~ti s~me illi~or me~abolites is sh~v.-n in T~.ble l
and is b~tsed on a study <~f eleven s~loker~ [171 Irot~s.3'-ffyd~oxycotlnin~ w~. lh~ I~lOSt
~bt~nd;ml ~tin;iry ~)lct~boli~¢ followed by ¢otinine-N-glacu¢0nide ~ntl cotinine Glucurt~nide
coniUg~leS acceunted [br app~oxlt~ately 3(1~.~ of all detect¢~ n~etaboli~es and Unn~etabolized
~llcoline fim~lcl in ~mnkers' urine I..~rge inter-individual variabilizy in tile total amour~l ¢,f
nicot~lltt excreted ar, d ~lle relative ab~.mdances of Illctz.holil¢$ '~as observed arl~on~ (here
s;llt~ker~ "]'hi~ ~'ati;~bihty ~llakes it ditt"*cuh to deten ~inq tota~ nic~tlne ab~vlpti0~ based
Ola the
Ille3.~tlretlle~l! O~" ~1 ~J.gle ntctaboli(¢ A~ m~'t~ods evo/ozd to determine all Icrlo~n
mel~bolitea,
5a64?l.faO7
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as$¢sxlng (<)(.~l nicDfillc u~I~ke hy 111on(tofifl~ ufifla:~ ¢~cFetio(I ~ ntcOlif*e BaG i[$
m~l~o)~leg
bee;role I t'~ib)¢
Aqal_~l M~tb, o,h,. ~Dg~i~Ncotlne ,~*~.~.~WL M.uly different o~thods
b~ve been used fi~t detet~inalion o£ nicotln~ and c~tdlir,¢ in hiolllgi¢~l fluids but only a few
)aboralories have rcporled melhods Ib~t deteIlnit~e nicotine, ils l)/~)o~ I))elaholltes (tr~J.s'-3'-
hydroxycc,tlr, lne, c~tlnirte, a~d their r~sp~cdve glu¢~lo~fid¢ conj~tgates), and s~vera~ minor
ones Gas chrnmatography (GC} ha.~ been reliah(y u~ed for sol;le time to de¢~rmi,~e ~ic.otln¢
a~d cot)nine in b~Ological ~%id~ [30-32]; bo~ever, som~ of th~ r/icolln~ me~abo]ites ~ud) as
nicotme-N'-oxid~ and the phase II met~.bo~ites are therm~ly ~lns~able an~ not suited to direct
atlaly~is by CK!. Ana;ytiea~ schemes using GC haw been e~:p~ded and impor~nl metabolit~
socb a~ nleotlne.N'-oxido [33] and ~ra~z~-Y-hy&*>:~yrofinir.e [121 b~v¢ be~n added in uepar~te
a~aty~es that involve deriw.fization An excellent GC method has been developed that
~c¢ounts l'or ni¢ollne al~d i~ two major urinary met~bolites, corinine and Irunz-3'-
hydroxymtinlne, i, asinglechra(~mtograohlean~bsis[J4] Thisme~od. inconjunetionwith
hy&ub's~s to free conjugated comi~unds, provides ~ rnean~ of aecclunlitlg for allnost all
nicotine abso:bed by sn~oke~. High performance liquid chromatog[aphy (HP~.C) ha.,~ beetx
~s-ed to determine mcotiae and cotini.¢ in hiak~glc,~l snmple~ witho~! dcrivatization {35~2]
tlFI.C method~ u~e~ in conjunctio~ v.lth deHvati~ation ~i',h 1,3-die'.hyl-2-thiobarbhuric acid
have been used ~o delerl~ine nico6ne lad up t~ t~'elve n~etaboEte~ in the t,rifle of amokcrs
[43-461 A Oo*se*'thl method de~eloged In our laboratory combine.s ~oLC witl: (he specilic(t)
of Ihermo~pr~.y nl~s~ speclro~*etry [,a7] ~d has bee~ ~pp}ied to study nicotine ~plake ,rod
metabolism in ~n~oker~ [17]. Am in the GC method mentioned above, whel~, used. in
coriiullcto)n wifh byd~(y~is to free co~ljugate~ compoands, almost ~l( ~rf the nicotine ~h~orbed
by ~mokcrs czn be dete;rni~ed by this LC/MS method Specific H~LU m~bod~ fo~ the
glucu~onide co)ljugates o[ cxothlin~ ;~nd ~icotine Ilzve been devel~lped in order to confirm their
structtwe and provide direc~ t,~¢t~)d~ of analys~ [14, 26. 29. 4$]. Iramt~as.~ay methods.
thtlugb limited in the ii~mbet Of metubolhes they ¢a~ dele~mlne, have pro)yen set~sifive ~o
~icotme znd il~ metabolite~ (49-~21 Cr~s-leaCti~¢tt~' of eotirlb~e anlihodie~; witll ~tl)t~r
mcolbzc IlzeI:tboii(es has been qu,~mified ISt, 54) A~ rexearcb colltintl¢'~ ill ~bi~ ~F¢.~I~ it
i~
possible that at~l~bodi,.~ vet-/ spec~c to ce~ain tT~ct~botite~ ~iH be developed
536471608
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u[Itak¢ ~Sl¢lg mclab~li¢ ¢learatzc,: da~ ahlathcd ~C~cr intravenous infllsian ¢'~ tricotine and
frora
bl~d aE~d t~tit:a~ mcotine goncerdlaIkm~ v.,a.~ devel¢,~ped by Bcnowit.z and Jacob [551 "lhls
rngth~ld Was t2omprehcnslve in esdtaladng daily al¢odne but required stl/~jeet re~enticm ill a
clinical watg, a factor that Nay have influenced the restllt~; due to additiLmal 5tr~ss or other
variables r¢laed to confinement. Nev~rthet*ss, lhis melbod has previd~d useful data in
$IadyiJ~g nicolil~c up!ak¢ flora nIllnbdr$ of cigarettes ~f',loked 156}, n~r.ofi~e pharmacokinelks
[57], and nlcotine uptaku from cigarettes versus the tlal~dermal patch [581. Similar ic~ults
have also bcct~ ctht~incd using blood colimtl¢ eae~.~ure:nent~ to estimate nicotine uplake {5~]
An inlpmved ~pproach would determine, tot~I n[r.odn~ uplake using noninvasivc
sampling. (ittl~ or no confinement of ~ubjec~, and [gt[~ or no variation in normal I~ks or
sm~lkillg hNmvior Smeki;Ig is a practice that is p3rl of a daily Io;~tine and the less a stt~dy
all~cts a Stlbject's wutin¢, the Lnor~ Iikely the study wilt reflect mlrma] smokil~g behavior and
IhuL n:m~)al nicotine uptake Pharm~ol0gi~al s~;dle.~ ofsmokillgbavedemo~straltM that
nicotine cxpo~u;e is not intermittent, bgl rag:er a 24 b per day exposure due to i~
~ccumuletlon in the body [60]. Actlv: smokers achicv¢ a s~¢~dy-s~arc level oF nlc~tlne in the
body thai dinlinishes only during sleep periods Thus, aa ideal method for nlc~tine uptake
wotlld moaitor al/output of nlcoti~= a~d its various metabolic rectus over a norraa[ 21 h
period for ~ smoker. Th~s point brlngg u~ back 1,5 urin,lry excrelJon t~l" nicotine and ik~
metabolizes and adcance.~ in analyti¢~.[ metkodok~gy described ab~ve
A rcvle~v of quantitative analytical wethod~ for total nicollne uptake sbov, s tblt very
high pcrcc~tag~s can be ~.chiev~ Kycrematen el a[ using radio-labeled nicotine ~tnd
rao~li~oring 9 tnetaholiles, 2 of which bad not pce~.iously been identified, demonstrated that
rect~vet'," wa~ g~ealdr than g0% in hum~s Ill} gcaov, it~ h~ sbown that major phase I
metabo[lle-~ alo~g ~itlt unmetaboliz,*d nicotine account for a~proximately 65~6 nf abs~',rbed
r~icOttne in snloker:~ lril] CUt'vMI et al demonstrated Ibltt a l~r.qe portion of nicotine
mctahnIism i~ through phase I[ precesses and tbal Ibe lice a~*d ~onj.ga~ed ['orms of nicotine,
cotinine ,and 3'-bydroxyt:otlnine, along with the N-o;*ides of nicetioe .t;Id colininc. ,~co~2nl
i)l more than +)fl% of absorbed nicol[ne [121 Thelcfbr~, method~ lhat dUtelt?line both ph~-~e 1
&nd ph;~s¢ II ~lrin*~y metabo!it~ r~f nicotlr~¢ m)d :l)clude minor ;nt:tabolJte~ ss~ch ae
nicotine-
536471GO9
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N'-ox~dc appr~ach ~1 nlcofin~ accountability Such high rccow'n~s il~ urine oll'e~ the best
m~ns ~r precise quasi'ration of ~ic<~lln~ upz~k~ by hurm".ns [32. 61]
Wc have incc~rpora~cd this unders~nciinS of n{cotinc mel~ohsrn itll~ a rnelh(~d fo~
de~erminillg d~il¥ ldcotinc uptake by s~loker~, l~ c~l b~ assumed that~ oil a ~aily I~si~, a
regzdar ~mok~¸ i~ach~ ~ sleady s~ale of ,ni~olia~ Con~cqu~nl]y, ~h~ al~lour~ ol" ilJcodnc
~ptake is ,~qll~l to th~ ~nlounl of nic~gnc and i~ nlc~abolites excreted by the smoker l:mm
~tld nlo.~line OUtput in "~4 h ll~iI~ sa~'nple~ ~.nd lhc number of ciSar~t~cs smoked pet day, we
i:ai~ c~tiI~llitu a r,i¢oliil~ tlpll~ va[tl¢ th~t ~flccts what dt¢ ~n~okcr ~bsorh~, t~n a.~eca~e,
~r(~I1
~ac~ c~a~'¢(l¢ T}li~ i~t~g~a~gd valtt<~ tlatlKal}y a¢c~u~ll.s far SIllokln~ bch~vi~tr va~'i~tion~
duHn~ Ih~ d~y An~lysls of 24 h urioe specimens to d~termlnc daily nicotin~ upla~e by
.~okcr~ has the ~.dva~lagc o~" h~ing Bon[nvasivc and permits ad llbi~m ~.moking by subjects
with minlrn~.l imp~t 0n their d~ily routines
T~ h~tt~f u~der~tand ~,h~ rclalionship b~twccn FI~ niccti~e yi~Ids and actu,~l n~cntine
upt.~k¢ by smokcr~, ~¢c apt~lied the above m~hc~&~lo~y t~ s~dy ~.i¢o~iae u~takc i~ 13 ~mol<cPs
thai spa~ne~l four p~od~c~ StOOps; I n'.g "tar~ (1MG), uIIr~-Io'* "l~rr' (ULT), £~ll-flaw~r lo~
"tat+ (F~t.T), and f+tt flavor (FF) d++r+tte smokers The~c ¢ig+rett+ ¢a~clries Md ~lean
FlrC nkolil~e yMds ~ li~led in TZ~I¢ [l "l'h~ suL~jecC~ ail stroked their usua~ cig~ret'~ brand
ad h61nm~ ~d submltt~d a 2g h uriB¢ sampI~ fi~r total nicotine uptake deteuBinaIion d~ring a
period h~r wl~eh the iluraber of cigarcrlea smoked was r~cl>~dcd
~J~ Thirt~-thccg adult volunteers be~'o~r~ 26 and -~O )'ear~ of age parli~ipateg in ~hi~
shady Suhjecb r~celved con~p~a~allor, fi:r lh¢~r p~rtJripa'iolL I}:~ purpo~c of Ihe ~lll,~y ~,~_~i
not r,~vcaled to the subjr~c, ts. The sub)ects i~.¢luded one fema!~ Caucasian, t~ne Fc~aic Aflican
Americall (both F[: snl~ker$), and 31 mal~ C~uc&~ia~t~ Subjects gave their informed cot/sent
prior to p~llclpating in the Sil~dy and ail prc~c~dur¢,~ used vcerc approved by ~ human reaeareh
review b~ard 'l'}:e conseal Ibrm described the proceth~ Iobc u~od a~d Iho aleasu;elllCllI,¢ t¢~
be made. hul ~li(l not dis¢los~ the purpose ut" lhe tc."~t~. The IMG, ULT, a,~a l",~ur ~,1' ~hc
FILl'
smokers were recruited g.s parl of ~ product-swltehlng sKIdy ,~r.d 4~( da~ us,ad h('r¢ represen/
364 1610
~s1-1~-~ 1~,$.~, Ft~Ot~, ~.J, b'~l~UL.t~ ~ ~ ~,~ ,7, , .--
6
s+nokln.q behavior prior ~.o ~.ny product ~wit~:h. '1-~o ~f the FELT snlokers and the FF
~moker~ were p.~r~ c~t* ~r~othcr study '.~h¢~e ~d tii~un sm~kitl~ ,,v~ requi~'od and 24 h tlrine
~.~mp)~ were ~ol~cl~d Ex~pl f~,r lh© IMG splicers, lb~ stlbjects ~ere recruited ~om "wi~hln
K J P, cyn~lds '[oba¢co Comp~,ny t,hro~gh i~lern~[y advertised volun~er request-~, ~r ~moke~
of ~pc~lfie typ~ c~f ¢ig~re~ "]'he IM~ snloker~ were recr~d!~ by random telephone
scree~lin~s fl~m a local popul~Jon (Wir~t~n.Salenl, NC) "lw~ ULT smokers inadvertently
misclassified thems¢[v~, as FELl smokers but were iflctuded in fl~e ULT group (ULT subjee~
12 and 138 Subj¢ct~ were ¢onsld~2tcd ~m~kes~ if they said they p~rmally smoked 20 or more
cigarctles per day. AIr subjects "~erc required to smoke their uzt~al bru~td of ci8,treltc
(cigarettes were not supplied to the smokc, rs by {be experimenters) as ¢llt~ch s~ they desife~,
ret~nd th~ number of cigateltes smoked, aM collect ~I[ their urine over a 24 h period
Subjects ~ho were not able to nicer these requirem~Ia~ were excluded from th~ s~ldy Each
g~p was stz~die~ ~:patately w~tb shghtly differenl colJecfioll pr~t~c~ls ")'he IMf~ az)d UL'f
(subjects ~-I I) smokers recorded the number of cigarettes snloked d~.ily ¢~er ~ one ~eek
period attd ~ub~tllt'~ed lilr¢~ cO~e,~Jtive 24 h urine aalnples an the I~riaJ Ihree day~ of that
week "1 he F]rLT, FF, and two LILT ~,m~)ker~ recorded lhe purnbet of eig~dette,~ :~mok'~ for
one to three tiays and c~[[ected a singt¢ 24 h urine sample on tile fi~al day Fo~ all the
smokers itl this st;ldy, the 24 h urine volun~e~ ran~d l~om 5518 to 48218 mL wlth an average
of 20~0 t 9t)0 ud, The FTC r, ic<~tine ratings of each s~hject's cigar~tl¢ brand (see '1 able lI)
were taken Iiom the 1092 Tobacex~ Instittf¢ Testing I.aho~atory Report [621
Procqdure .~amp~es for the IMP, FFL'I', and FY smokers v,e~e prepared and analyzed
accorlhng Io n i~:lldit'~catiou [17] ol'a published LC/MS method [47[. "[l~e ULT smoker
,~anlpIcs were an,dyzed by a modification [6)1 of~ /~2blished GCAX|8 meth~,d [3,'~] shown ZO
give c~mpurabIe nicotine ~ptake data to the LCIMS metbnd ta both medlods, nicolin0 and,
I~tahtllit~ concentl'at~o~ ~,~ere ~.t{ttl~¢d to produce a io(~l r]i¢otine ¢~aeer~tratiorl This
~l[ti~
wit,~ multip]ied by t~e 24 h urine ~o]ume to ~ive the t~ltal anlounl of nicotine uptake I'o~ 24 h
The daily ni¢o;~ne uptake divided by tile nurt~b~.r of ci~areues smoked ~uve the nicotine
~pli~ke per cigarette
Ihc data werg ~tati~lically analyze~5 b3, ~¢ver,~l methods Parred I-te~ls were tl~;etl 10
Co~llll~tl~ I:'|'(~ at~d ille~/ufgd yields per ci~rolr~ fl>r Jo~r~lle groIl~ ~ttld 311 ~mokels
together
53G471611
The ,~Emips ~u~ al~o ~mp~r~d usmB Duncan's M~llipl¢ Ran_~¢ 'l~t R¢~t~si~n an~lys~s
was u~¢~ I~1 ~gs! ~t TIIc ~xibteil¢~ oi" a lillcar l~la~Jn.~llip ~clw¢cfl FTC yield and
ltlcas~rcd
dill~enc~s il~ nicotine uptake that mighl be cxpect~,d ~ a ffmcti~n ol,'~:lC yi~(d. Finally, li~e
¢or(elalloo b~t~o¢~ nicot~n~ ~lpI~kc a~ ~)~mb~of ciga~cI!es wa~ de)ermia~J $ige, i~cat)ce
w~ d~lltlcd as P ~ 0 05
Group avcr~e~ for measured n~c~i~¢ up'~2~c azt pie.seated i~ ]'ab)e I! with 8rou~,ia~l ba~ed
on FTC ~,ie~d category Nicotine 0ptak¢ iS rep~med en a pcl cigarette (n~ ',~cig) ~,a~ d~ily
(In~2-1 h) b,~.i~ Th~ number of cisaI¢[tes arid nico/~r.¢ uptake data per 24 h were b~ed ~rl
tbreu day average )'~)r d~0 )MG a~d ULT smokers ~.nd or) ~ s;n~¢ day for ~c FFLT ~r3 FF
sl~oke~s The l:l'C nicotine it~ mgt24 h wxs calculated from thc ~umber of ¢igarctt~s smoked
~)uhifll~cd by tl~ FTC" nicotln¢ yield in m~tci~ret~ "1'h¢~¢ FTC v~lues ~('c COmpared it~
Tabl~ II with the mc~%ur~d nlzotin~ t~pt~ke a~ m~,24 h and also a-~ m~clga.ret~e c~)~ulated 10y
dividi:~g t(~ mca~u~cd m~24 b value by the number cl'cig:~reltes smoked. In order t~
,.~mpare actual versus predic;ed r.icoflne u/~take, the daiiy me.tiled i3,icot]t)¢ ll~L~k~ ~lld
I~l.~t
ptedlcted by FT(; 5,]~Id ~.r¢ expr~sed ~s ~- t~.tio
At, (i~'Cl~,'iew o/" "]'~ble 11 suggei~ l~rge vari~:km ifl ~z~¢)klng bch~or ~ rc~ectcd in
nicnline uplak~ ~nd number of cig~rett~ smoked There was a broad rallg~ of" daily mcotin¢
uptak~ ~ilbin eacb group (I-22 gig for I.'vlO, 4-g2 Illg 0)r LILT, 13-3g trig t~r YFLT, and 21-
60 mg for F|:) wilb s~ightly ~.'u-rowef rClalive rn~s wh~ cor~tcd for aumbe/o.f ci~rtlt~
smoked (0.Ol~-ll 37, (~ ]6--0 ~2, 0 37-0.~6. and l~ ~3-1 62 t~g, cigmctxc, resl~ectivoly) The
f/ore 34 to 3"7 Th= average l~.tio~ t)f 0~¢a-~ufed ~icotinc uplak~ to f~1'C (~icotlne yi~!d ~
~isted
in I al:le It w~re ne~ unity fo~ FF, FFLT. and ULT ~mokels, bm inctt)aScd to 1 64 ± 0 ~2 for
the IMG snloker~ Ahhou)3i; IMG SlllOk~lS ~l~ a ,~rl)t)~ Im~dcd to c~c¢~d FTC ilr~dlcfior~
lm)le thal~ the! others, lilly SLii[ ~ccelv~d si.u.mfi~tltly [c.~'~ rd~otTne on t~v~:ra~c co[1~parcd
to tbc
olhe~ ~r(It)p~ o~ a per ¢igareil(' ~d on ,') dai',y ~i,ls)s ] wc~ly-oJle of 1})¢ 3~ sn)o]¢crs
(t,4%) in
5364 161
8
th~s study al,.~od,ed mo~c fl~an file ~TC pret~ict~d y,~id of nic~,dne and 12 (J6%) fcccivcd i~s
M~tcd mco+,~ne uptake m m ~dcEg~rc¢~c w~ ccm~a:cd ~ ~ H~" yield usmg ~
fl~e FTC ~ b~cd ~n the level o~ v~b~y ~d ~c numb~ of ~bjc¢~ ~sted
N~ u~e am~ th~ four ~oups w~ compa~d on ~ per d~ette a~d daily
s~gn~fic~m ~ff~.~c,c~ b~w~c~ the ~P ~ ~ ~ ~ ~oup~ ~h ~e~pect m d~ily and
i-,er c~¢t'~ ~c,~t~ uptak~ The ULT ~d FI~LT .~m~k~ ~ow~ ~ ~i~aific~mt differ~nc~
~om c~¢h ~hcr m ~i~ez cate~Py wMch is not s~prisi~B smcc ~ average FTC yi¢Id~ of
diffc~a~ ~i IMG smoke~s oa a p~ c~ett¢ b~i~ but ~:fiy k]c~ ~rs wc~e d~em
~om IMG ~mokc~s i~ daily aico~ uptake.
A~m~ ~'~adty bel~a F]~ ~d a~d me~c~ n]amn¢~ketcs~cd~or
smukc ¢i~a~¢ites ef h~hcr FTC yield)The data ar~ plotte~ a~ a r u~/¢fon tff YTC yield ia
F~gu~¢ 2 |:i~re 2a shows aicotme ttprake a+~ rng,~4 h lb~lhe md~vi~al smOker~ and Flgur~
2b diet?lays @~" avc~agc~nd~umdarddcviallcmsf,~re,~chp~od~ct ~roup Lirle~rregrc,~skm
aIlalyM~ of file data ~a.~ pel~ormcd and I1~e tcS~ILS ar~ }i~le~ o~, each p!ot. ]~e-~e plot~ ref]~I
~hc ~vid~ v~r~atioas ¢~f nicotine uptake withizl e~ctl BW~p t~fsm~ke:s "['h)s variability is
SOlt~cwhat dtluml~k~d w[len n~¢olill¢ uptake wlu,:~ ~e ii~-igahzed to ~he ~ul~lb¢~" of
¢i~ar¢lt¢~
smoke6,~s ~N)w~l ~n Figures2cand2d An6 y~l, lhe ~ri~p mcans lbrnJc~ti~ iip/ak~ ~bo'~ a
si~fi~al~I imcur rclatlo,qship with ',ke F TO ~k,~il~c yield (p ~" 0 05) fo~" b~th nlcofine uplake
p~ 24 h a l~d p~r c;Bar~Uc Note that lhe.xIopcs in th¢~c p!ms ar~ po~idvc, indlca!ill~ a~
incr¢,ls~+~ r,,lat~nsb;p ~,¢th FI'C yie)d
The eorrelauon bet~-een measared n~eoli~e upc,~k~ an5 tlumbcrufcig~*rctte$~nloked
wm~ dctcrminc'd '['h~c ~¢o pararncler~ were hLchly ¢orr~l.tcd f~r IMG smoker~ (Pcarma I~.
l'~flk,x~e~hy I l.l ,,|l~kers (K~0.~7) TIle vcr~ h~h c~melation b~ IMG~;Iloke~s, ib~ |uw~
yicld ci~3,~eltc gi~.+up, sug~e~,t~ that thcuc s, mckcr~ ach~'~c incrca~¢d snlokc e~Pt~ure by
:~mc~k~.g ,igt¢.t~-lnurltl.~¢ro~,:igare~:es.~olb~'"¢~ul~f~c~<~i~ag' or~o mdi~dual cigarc{t~"
$BG471613
