Oral fluoride retention after uso of fluoride dentifrices

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Cafies Res 1991 ;25: 123-129 © 1991 S. Karger AO, Basel 0008-6568/9110252-0123 s 2.75/0 R.M. Duckworth, S.N. Morgan' UnileverDental Research, Unilever Research Port Sunlight Laboratory, Bebington, UK Key Words. Dentifrice Fluoride· Kinetics· Monofluorophosphate, Oral f1uoride retention· Reservoir· S,divary clcara ncc Abstract. Fluoride is the only extensively clinically proven means of reducing dental cáries. Despire a !arge bodyof epidemiological data on the effectiveness of t1uoride, delivered in the form of dentifrices, mouthrinses, drinking water, etc., the precise mode of action of fluoride is not completeIy understood. The purpose of this p.lperis to report an investigation ofthe link between oral f1uoride levels and applied f1uoride dose from denti- rriCt:~, Hum an sulivary fluoride clearance studies and equilibrium baseline studies 01' fluoride in saliva and plaquc have been carried out with denti~'rices whicl: con~ained 1,0?O, I,50? ~nd 2,5?0 ug fluo~ide per gram as , sodium monofluorophosphate, After a single brushing with a fluonde dentifrice, salivary fluonde decreased 111 111'0 distinct phases: an initial rapid phase which lasted for 40-80 min, depending on the individual, and a sec- ond slaw phase !asting for severa! hours. The Jatter phase is be!ieved to be due to fluoride released from an ora! Ouoride reservo ir. During regular repeated use ofthe test dentifrices, the equilibrium baseline f1uoride concen- ralion, attained in both saliva and plaque between one application and the next,increased significant!y com- pared with placebo values. Such e!evated baseline fluoride concentrations also increased with increasing Na:FP03 content 01' the dentifrices. The presentwork supports the concept that labile f1uoride, stored in an oral [luoride reservoir at the time oftreatment application, may maintain a prolonged protective effect against dental caries. I I Many countries have experienced dramatic reduc- /' . , lions in caries prcvalence ave r the past 15 years or so. "fhese reductions have often been related to lhe regu- lar use ar flu(ji'i~·e (entífI'ices [Murra} and Rugg- Gun n , 1982~ Matthtilet;· enson er ai., 985; Rolla and @gaatd,. i987}, the niajol'ity af which con- !aio sodium tiidtiôfluotophos hate and/or .!odium nuo ri as the s0utces of uQÜde. Despite the large arnount of epidemiological data on the anticaries effectiveness of fluoride, the precise mo de of action of fluoride is not completely under- sto od . There is 3ubstantial evidcnce that the presence of fluorÍde i li the í1l'outh encourages the remíneraliza- t~ar1 I lesiens [Gelharc.! and Arends, 1984; Mell- berg et al., 198$, 19S6; COrprOJ1 et al., 1986: de Kloet J We thank DI'. P.T. Whittall for assistance with cornputer pro- gramming. et aI., 1986; Goorhuis and Purdell-Lewis, 1986; Schâfer, 1989]. Saliva is supersaturated with respect to the hydroxyapaÚte of tooth ename! and is a source of c~lciu;n-and phClSpnat ·OU~ (o tbe_re ir õ(ear.ly enarnel lesions. Certain authors have suggested that fluoride, even at low concentrations, Ís necessary in the oral fluids to õbtain rnaximum carie's inhibition and have con- e udedth<rt continuous or frequent elevation of the flu;ride concentratiõOin the orãIfluid; wouTclbeãd': --- ~ - -- -- ---; y"'antageous [Fejerskov et al., 1981; Ekstrand et aI., 1986; Featherstone et al., 1986}. The retention offluo- ride in the mouth after application of dentalprodUcts sucl;aSdentífr~ and ~OUthwashes may be asso- çjl!kd wíth an oral fluoride reservoir. Such a reservo ir ma serve as a store for fluoride which reIeases its co teIl!..s into saliva gradually and thereby potentially rnaintains a degres of protection against caries for a ,---. ,.. - .. :.~\ . , . .i ;

Transcript of Oral fluoride retention after uso of fluoride dentifrices

Page 1: Oral fluoride retention after uso of fluoride dentifrices

Cafies Res 1991 ;25: 123-129© 1991 S. Karger AO, Basel

0008-6568/9110252-0123 s 2.75/0

R.M. Duckworth, S.N. Morgan'UnileverDental Research, Unilever Research Port Sunlight Laboratory, Bebington, UK

Key Words. Dentifrice Fluoride· Kinetics· Monofluorophosphate, Oral f1uoride retention· Reservoir·S,divaryclcara ncc

Abstract. Fluoride is the only extensively clinically proven means of reducing dental cáries. Despire a !argebodyof epidemiological data on the effectiveness of t1uoride, delivered in the form of dentifrices, mouthrinses,drinking water, etc., the precise mode of action of fluoride is not completeIy understood. The purpose of thisp.lperis to report an investigation ofthe link between oral f1uoride levels and applied f1uoride dose from denti-rriCt:~, Hum an sulivary fluoride clearance studies and equilibrium baseline studies 01' fluoride in saliva andplaquc have been carried out with denti~'rices whicl: con~ained 1,0?O, I ,50? ~nd 2,5?0 ug fluo~ide per gram as

, sodium monofluorophosphate, After a single brushing with a fluonde dentifrice, salivary fluonde decreased 111

111'0 distinct phases: an initial rapid phase which lasted for 40-80 min, depending on the individual, and a sec-ond slaw phase !asting for severa! hours. The Jatter phase is be!ieved to be due to fluoride released from an ora!Ouoride reservo ir. During regular repeated use ofthe test dentifrices, the equilibrium baseline f1uoride concen-ralion, attained in both saliva and plaque between one application and the next,increased significant!y com-pared with placebo values. Such e!evated baseline fluoride concentrations also increased with increasingNa:FP03 content 01' the dentifrices. The presentwork supports the concept that labile f1uoride, stored in anoral [luoride reservoir at the time oftreatment application, may maintain a prolonged protective effect againstdental caries.

I

I

Many countries have experienced dramatic reduc-/' . ,

lions in caries prcvalence ave r the past 15 years or so."fhese reductions have often been related to lhe regu-lar use ar flu(ji'i~·e (entífI'ices [Murra} and Rugg-Gunn, 1982~ Matthtilet;· enson er ai., 985;Rolla and @gaatd,. i987}, the niajol'ity af which con-!aio sodium tiidtiôfluotophos hate and/or .!odiumnuori as the s0utces of uQÜde.

Despite the large arnount of epidemiological dataon the anticaries effectiveness of fluoride, the precisemode of action of fluoride is not completely under-stood. There is 3ubstantial evidcnce that the presenceof fluorÍde ili the í1l'outh encourages the remíneraliza-t~ar1 I lesiens [Gelharc.! and Arends, 1984; Mell-berg et al., 198$, 19S6; COrprOJ1 et al., 1986: de Kloet

J We thank DI'. P.T. Whittall for assistance with cornputer pro-gramming.

et aI., 1986; Goorhuis and Purdell-Lewis, 1986;Schâfer, 1989]. Saliva is supersaturated with respect tothe hydroxyapaÚte of tooth ename! and is a source ofc~lciu;n-and phClSpnat ·OU~ (o tbe_re ir õ(ear.lyenarnel lesions.

Certain authors have suggested that fluoride, evenat low concentrations, Ís necessary in the oral fluids toõbtain rnaximum carie's inhibition and have con-e udedth<rt continuous or frequent elevation of theflu;ride concentratiõOin the orãIfluid; wouTclbeãd':--- ~ - -- -- ---;y"'antageous [Fejerskov et al., 1981; Ekstrand et aI.,1986; Featherstone et al., 1986}.The retention offluo-ride in the mouth after application of dentalprodUctssucl;aSdentífr~ and ~OUthwashes may be asso-çjl!kd wíth an oral fluoride reservoir. Such a reservo irma serve as a store for fluoride which reIeases itsco teIl!..s into saliva gradually and thereby potentiallyrnaintains a degres of protection against caries for a,---. ,.. -

..:.~\. ,.

. i

;

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·-124

~60 l50 Uo

o:> li> •4-0

30

I '.~I

DuckworthiMorg~ ~'-------- --,~!~I~buffer using previously described procedures [Duckworth et al ' '~1987J. Saliva samples collected witl in 3 h after dentifrice apPhc". "

tion v:ere either treated with perchloric ~cid 01 incubated at 37 C ~l.·,.overnight morder to ensure that any FPO'i ions were hydrolyzed Ia ffiiF- before fluoride analysis, A feasibility study confírmed thlj I"'known arnounts of Na1FP03 added to whole saliva were COl1venl'd . 'pcompletely to r by lhe latter procedure (fig. I). "

~'

Oral Clearance Studies '117-10 adult subjects used a non-fluoride dentifrice at home fOral

least 10 days prior to, and during, lhe experimental period Foreach test, lhe subjects brushed with 1,5 g test dcntifrice for I miospat out lhe dentifrice/saliva slurry, and then rinsed their mOUt~

for 5 s with 10 ml distilled water twice. Mixed saliva samplc" .(> 0.8 ml) were collected both bcfore dcntifricc application and a; tregular intervals Cor several hours afterwards, At least 2 day! ~elapsed between applications er each test ?entifrice. Subjecis welt ~lasked not to drink tCJ 01' cal during iest pcriods, ~

'",1R

oE=:: 10

li.

"'Q,

ti:: O +--------.--------.-------r-----r-----,O 5 10 15 20 25Time, h

Fig. 1. Break down of FPO~' to F" in hurnan whole saliva incu-bated at 37°e. Nominal initial FPO~- concentration 52.6 umol/I(I pprn F). Symbols refer to different experiments.

prolonged period. Fluoride which is present in theíii'Oiith in a labile form during a cariogenic challengeis JikeJy to be the most bcneficial.

The work reported here seeks to determine whetherthe amount of l1uoride retained in the mouth is suffi-cient to maintain a significantly elevated level of fluo-ride between 01 e application of a dentifrice and thenext. Oral fluoride studies have most often involvedmeasurements ofthe fluoride content ofwhole-mouth(rnixed) saliva and of plaque. In this work two typesof measurements have been rnade to investigate theconcentration of fluoride itUilli..Y.:J bét;ecn b[1lshing~~it l-dentifoF-'. Oral clearance studies have moni-~ - -tored the decrssse in fluoride concentration with timeafter a single dentifrice application, whilst equilib-rium studies have monitored changes in the baselinefluoride concentration during regular, repeated use ofdentifrices. The dentifrices used in the studies re-ported here contained sodium monofluorophosphate~ .

as the fluoride some.

Materials arid Mefhods

The test dentifrices contained 1,000, 1,500, and 2,500 Ilg fluo-ride per gram as Na)"POj in an alumina base and were identical toformulations tesred iü a 3-yeàl' caries clinical trial [Stephen et al.,1988], Fluoride conteuts of saliva and plaque were rneasured bymeans 01' a fluoride lon: speciíic electrode in the presence ofTISAB

Equilibrium StudyThe protocol was similar to that of a previous study involving

mouthwashes [Duckworth et al., 1987J. Briefly, 7 adults used a nOnofluoride dentifrice for at least 2 weeks prior to the use of the teM

dentifrices. The subjects then brushed with each test dentifrice dailyfor about 4 weeks. Samples of saliva and plaque were collectedonce per week, at least 18 h after the last brushing. The subjcclswere not exposed to any other high-fluoride dose during the study,

F, = A exp (-at) + B exp (-~t)

Curve FiuingBoth individual and mean oral fluoride clearance curves wcrc

fitted by computer (SAS PROC NLlN) using a non-lincar regres.sion procedure [Marquardt, 1963] to the biexponential function

where F, is the salivary fluoride concentration at time t, and A, e,B, and ~ are model parameters. In approximation A and B are lhezero time intercepts, and a and ~ the slopes, of lhe first and secondclearance phases of clearance curves respectively. Equation I is lhesolution for lhe so-called two-compartment open pharmacokinclicmodel originally applíed to lhe analysis of drug clcurance Crornblood [Wagner, 1975J, Arcas under each clearance curve (AUC vaI.ues) were calculated using the equation

AUC = S F, dt = A/a + B/~o

(2)

The half-lives of each clearance phase were calculated using therespective expressions tl/2 (I) = 0.693/a, and tl/2 (2) = 0.693/p. !\

Results

Salivary Fluoride ClearanceThe shape of salivary fluoride clearance curves was

similar after a single brushing with any of the denti.frices tested. Typical mean data for 10 subjects whohad used a dentifrice containing 1,500 ug fluoride per

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...

livaFluoride from Dentifrices:;..--..,

r:lm as Na2FPO, are shown in figure 2. Total ionic, ~uorideco~centration .(F- +, FPO~- íons) is plot~ed on.dogarithmlc scale against time and decreased m twodlstinct phases. During the first phase, which !astedfor 40-80 min depending on the individual, the meani,;\livary fluoride concentration decreased rapidly~r(11!1ca. 200 to ca. 4 umol/L During the second phase,lhe salivary fluoride concentration decreased rela-

I 'Ii\'ely slowly and reached 0.95 umol/I after 3 h. As,:1 part of the dose-response study mentioned below, 7

I 5ubjects used the same dentifrice and the averageI, Ouoride concentration during the second c1earance

p asedecreased to 0.58 umol/I after 6 h.! The comparison in figure 2 between the mean

! ' e~perimental data points and the curve derived using; quation 1 indicates that the chosen pharmacokinetici modelis appropriate. The quality of fit was excellent

(r'" 0.999) and values of r2> 0.99 were consistentlyobserved for the individual c1earance data.

Results for à dose-response study in which 7 sub-jects used each dentifrice are summarized in table I in~ermsofthe model pararneters AUC and B. These pa-

meters are measures of the overall amount of fluo-ride in the mouth and the amount of fluoride asso-~iated with the second c1earance phase respectively.Linear regression analysis showed the increase inb'oth parameters with increasing Na2FP03 content ofdentifrices to be highly significant on an individualbasis (p<O.OOOi) The rnean AUC and B values forlhe dentifrice with a fluoride content of 2,500 ~tg/gIVeresignificantly difTerent from corresponding val-ues for the 1,000- and 1,500-flg F/g dentifrices(P<0.02; analysis of variance). Furthermore, the ma-;ority of individual AUC (6/7) and B (517) values~verehígher after use of the 1,500 ug FI g dentifricethan after use of the dentifrice with a fluoride content,11'1,000 !lg/g. efes'p'ife the rrtean difference being notstatistically significànt. AO mean B values were signif-icantly above the mean baseline fluoride concentra-[iOIlof 0.46 !J.l1101/1 rneasured in saliva sarnples takenbefore dentifrice application. The mean half-lives ofeach cleurance phase are also listed in table l. Thevalueof t 1/2 (2) for the 2,500-flg fluoride group was sig-nificantly less than the corresponding value for lhegrOUPusing a dentifrice with a Iluoride content 01'!,OOO!J.g/g (p < 0.05).

'o

::í Equilibrium Studyi The baseline salivar)' fluoride concentration in-

creased mark edly during regular, repeated use of flu-

125

200 J _"-----',r

100 ~

1 A

1.0

0,5 --fl----~ '----,---------;,,-----~o 50 100 150 200

Time, min

Fig. 2. Mean salivary fluoride clearance curve after use of 1,500flg F/g NazFPOJ dentifrice (n = 10). O = Experimental data (bars= SD); - = computer-fitted model curve.

Table 1. Dependence of clearance curve parameters on theNa2FP03 content of dentifrices (mean ± SD; n = 7)

Na2FPO, ParameterB AUC t,12(1) t,nC2)(F, ug/g) (F, umcl/I)" (mmol F/I- min)" rnin min

1,000 1.48 (+ 0.73) ]1.9J (+ 0.36) 9.1 ±2.2 244.9± 84.3(- 0.47) (- 0.30)

1,500 1.88 (+ 0.85) 2.22 (+ 0,42) 9.0±2,4 197.2±50,0(- 0.57) (_. 0.35)

2,500 3.03 (+ 1,43) 3.87 (+ 0.73) 6.5 ± 2-8 141.9 ± 34.8(- 0.98) (- 0.61)

a Values are antilogs of logarithmic mean values ofthc individualdata. The 2,500-).1g/g values are significantly different from lhevalues connected by lhe bar (p < 0.02; analysis ofvariance).--------------

oride derttifrices relative to a non-F control dentifrice.Figure 3 shows that the rnean salivary fluoride con-centration increased steadily to a plateau after about 2weeks of daily brushing with the dentífrice containing1,000 ug fluoride per gramo This pattern was repeatedwith each dentifrice tested. When brushing with a flu-oride dentifrice stopped, the baseline salivary f1uorideconcentration returned to its original value which hadbeen attained using the non-fluoride controI denti-frice. Table 2 summarizes the mean equilibrium pla-teau values obtained for each test dentifrice in bothsaliva and plaque. Both saliva and plaque fluoridevalues incrcased with increasing Na2FP03 content of

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r[26

~ 12l

'°1 IoE 0.8a,

LL'

'":n~ 0.6'"lf)

------------,.-----------,,-----------,o 50 100 150Time, days

Fig. 3. Me~n equilibriurn salivary fluoride concentration, mea-sured at least 18 h after last brushing, during daily use of Na2FPOJdentifrices (bárs = 50). O = Placebo; À. = 1,000 ug F/g;1,500 ug F/g;. = 2,500 ug F/g.

(4)

Gut E-f.{6[X.fL

Fig. 4. The Iate lir fluoride during and after dentifrice applica-tion. For further expi:'üiatiaii Sei: Disctrssion,

Table 2. Equilrbr1um oral fluoride conéentl'âtiOrls during tlreuse ofNa1FPOJ deritifrices (ntean ± SD; n •• 7)

Na,FP03

(F, iJ.gl ,)Saliva fluorideumcl/!

Plaque fluorideng/rng wet weight

o1,0001.500

2,500

OA3±o-.05Ct15±O.06O',8'4±O.05 },0.8'1 tO,09 .

1.46±0.271.76 ± 0.55L93 ±O.572.36:1: 1.20

Saliva values c6tiiktte'd by the bar are not signiflcaruly dif-ferenl.

i'lDuckworlh/Morg· !lI~1;'

\~!

the dentifrices. As reported previously [Duckworth tl ',,~

al., 1989], linear regression analysis of the individua;jplaque fluoride data gave a statistically significan;correlation coefficient of 0.433 (p < 0.025; F test). 10contrast to the plaque results, it can be seen from,!table 2 that the mean equilibrium saliva íluoride COr,.

centration tended to plateau at high fluoride dose.Nevertheless, regression analysis of the individual ~i\'data indicated a highly significant dose-respo-g, )correlation (p < 0.001). Furthermore, all mean ,salivalfluoride values for the Na2FP03 dentifrices were sigot; ,nificantly higher than the corresponding mean value I'for the non-fluoride control dentifrice (p < 0.01; anat. ,I

ysis of variance), and the saliva fluoride values for lhe 'i

dentifrices containing 1,500 and 2,500 ug fluoride per .!I,gram were significantly higher than the values for the lidentifrice with a fluoride content of 1,000 llg/g I>,i\\

(p < 0.05; analysis ofvariance), ~

iIDiscussion

The salivary fluoride c1earance studies have shoWn "Ithat.mo~e than one process is in~olv.ed in fluoride re.I.,tention 10 the mouth after application of a f1uoride ~, .dentifrice. Figure 2 indicates that cIearance curves ~l'were consistent with a two-compartrnent open pha-, imacokinetic model, This model assumes three firs], iorder rate constants which correspond to processes tfor the elimination of a therapeutic agent from one .compartment and for the uptake of the agent to, and .:release from, a second compartment [Wagner, 1975]. t

Following this model, a possible representation of Ithe fate of fluoride in the mouth during and after ap- iplication of a fluoride-containing dentifrice is givenin figure 4. Five stages are identified: (1) during brush.ing the dentifrice becomes mixed with saliva in thernouth; (2) fluoride species are taken up by the oral f

tissues; (3) after 30-60 s a major fraction of the ap. )plíed fluoride is lost from the mouth when the bulk of 'the saliva/ dentifrice slurry is spat out and the mouthis rinsed with water; (4) the remaining fluoride ismostJy lost from the mouth by swallowing or is takenup by the oral tissues, and (5) as the salivary f1uorideconcentration decreases with time, the release 01' fluo.ride frorn the oral tissues is increasingly favoured.

The above scheme is probably broadly applicabls 'to topically applied therapeutic agents and, for exam-ple, is similar to models considered for the oral dispo-sition of antíplaque agents [Gilbert et aI., 1987; van

t

Page 5: Oral fluoride retention after uso of fluoride dentifrices

rn liva F!uoride from Dentifrices:-.. ~ ----

~t derOuderaa and Cummins, 1989]. For completeness,II 'I lht: distribution of any ingested agent via the systemict " I blood circulation should also be included [Ekstrand1 c! al., 1986; van der Ouderaa and Cummins, 1989].1 The sequ~r fluoride uptake and release repre.-

,.t1~ stages 2 and 5 can be viewed as the storage~ase O(]1uoride (or monofluorophosphate)ir;-anatural oral 'reserv()ir~ Thus, the initial rapidj;!ilin saliv-aryfluoride~centration IS most "i1<eTyclearance of fluoride frorn the mouth by swallowingiísâ resilTt of Ifiecontiiiiious flow of saliva (stage 4).T~d~tive y slow, clearance phase is be-I~e dUe to fluo ri de, retained in the oral reser-\~pred~antl~in dentifrice a lication,\~sequently rel~~ed into the saliva (stage

').."Although the above interpretation may be simplis-tíc, the model clearly provides an excellent represen-tation of the observed salivary fluoride clearancebehaviour within the experimental error of the mea-surernents. ln aIl robabilit the o' eservo·· C_Q -

sistsof a number of microreservoirs, e.g., plaque, the~es of gums, tongue, and cheeks, and stagna-tion zones between the teeth, under the tongue, and inlhe buccaI sulcus. Recent in vitro work indicated thatlhe soft tissues might be the major reservoir for fluo-rrde [Duckworth and Jones, 1989a], as has been sug-gested for the antiplaque agent triclosan [Gilbert andWilliarns 1987]. Some authors have postulated thatlhe orally retained fluoride is stored ln the form of(alclUm fluoride or calcium-fluoride-like material~n et a!., 1981; R611a, 1988].

The contribution to whole saliva fluoride fromductal saliva after a single dentifrice application willbe smai1. We estimate [Duckworth et al., unpubl. ob-servatioh1 the arnount (lf íluoride ingested at the timeof dentifdce' application to be less than 10% of the ap-plied dose, •.e., <0.225 mg frorn 1.5 g of a dentifricecontaif}írig 1,500 !-lg F/g. Oliveby et al. [1989} ob-served that the maximurn elevation of the fluorideconcentration measured in unstimulated whole saliva50 min after ingestion of I mg fluoride was approxi-mately 0.8 urriol/I above the corresponding baselinevaiue. Th:Ís elevation decreased to 0.24 urnol/I after120min. Thus the contribution to the data of figure 2is unlikely to be more than 0.2 and 0.05 umol/I at 50and 120 rnin respectively.

The salivary fluoride clearance behaviour ob-served here is similar to the results reported by Bruunet aI. [1984] who foundelevated salivary fluoride con-

I ! I

127

centrations which increased with the Na2FP03 COI1-

tent of dentifrices for up to 2 h after application.Qualitatively similar findings were also reported byFinidori and Lamendin [1980]. Bruun et al, [1987] fit-ted cIearance curves obtained during the first 30 minafter dentifrice application using the Weibull func-tion. The present analysis appears to be generally ap-plicable for a longer time period, up to 6 h in thiswork, and is also more informative about the mecha-nisms involved in oral fluoride retention.

The present study has involved fluoride-containingdentifrices. However, it would be expected that themode! should be applicable to salivary fluoride clear-ance following the use of other topical fluoridé treat-ments. For example, there have been a number ofstudies of fluoride clearance after use of NaF rnouth-rinses [Aasenden et aI., 1968; Heintze and Petersson,1979; Bruun et aI., 1982; Zero et aI., 1988; Duckworthand Jones, 1989b]. The last mentioned workersshowed that equation I could be applied to such clear-ance curves.

The two-phaseclearance behaviour observed here .is similar to the salivary clearance of the antiplaqueagent tricIosan reported by Gilbert and Williams[1987]. These authors estimated the half-lives of thefirst and second phases to be 27 and 145 min respec-tively. The corresponding mean half-lives obtainedhere fo-;--fluoride are 8 and 195 min res ectively.SfeeOrly et a!. [1985] also found two-phase saliv~rycIearance curves for sucrose and glucose. However, itshould be noted that the initial phase described heremost probably corresponds to the second phase de-scribed by the above authors. This phase is also theunstimulated saliva cIearance phase for sugar mo-delled by Dawes [1983].

The equilibrium baseline fluoride levels attained inthe above clearance studies were very low « 1 umolF/I); in qualitativo agreement with Duckworth et al.[1987] who noted that the natural f1uoríde content ofthe drinking water in this region is relatively low (1.4 . rumol/I), Of crucial importance for the oral fluoride - '/

-"- i/reservoir concept, however, is the observation that thebaseline leve! itself was elevated during regular use ofnuoride dentifrices. 1n these studies fluoride ~ure-ments were made on samples of saliva and plaque col-lected approximately 18 h after a dentifrice applica-tion. The elevatíon in saliva is unlikely to have beencaused by systemic fluoride. Ingram and Morgan[1987] found that the f1uoride concentration in pa-rotid saliva was approximately 80% of the value in

Page 6: Oral fluoride retention after uso of fluoride dentifrices

I__________ . . . D_u_c_k_W.~

whole saliva from subjects who had used a non-fluo-ride dentifrice regularly for 1 month. However, theformer concentration did not change after repeateddaily use of a topical mouthrinse which contained1,000 ug F/g, unlike the whole-saliva fluoride value[Ingram and Morgan, unpubl. observationJ.

The relationship between increasing plaque flu-oride content and increasing applied dose is similarto that previously observed for NaF mouthwashes[Duckworth et al., 1987J. Birkeland [1972J and Main-waring [1976J also recorded increases in the plaquelluoride concentration after regular use of dentifricesê~taining 1,000 ll.g F/g, as NaF andNa2FPO,,;:;;spectively, reI ative to non-fluoride controls.'The mean equilibrium saliva f1uoride -concentra-

tions measured in the present dentifrice study arelower than those reported in a previous mouthwashstudy [Duckworth et al., 1987]. This difference is con-sistent with the corresponding plaque f1uoride data.Duckworth et al. [1989] suggested that the accumula-tion of lower levels of fluoride in p!aque during regu-lar dentifrice use than during regular mouthwash usecould have been because of either the different modesof application 01' interactions of lluoride with otherformulation components in the dentifrices. Either arboth 01' these possibilities could be responsible for thelower equilibrium saliva fluoride concentrationsfound in lhe current dentifrice study.

The tendency of the saliva fluoride concentrationduring the equilibrium study to plateau at high ap-plied fluoride dose was not observed with the corre-sponding plaque lluoride concentrations nor with thesaliva lluoride concentration observed in the previousmouthwash study. The reason for this behaviour isnot understood. The fact that the clearance curve pa-rarneters after single use of the dentifrices (by thesame subjects) did not plateau at a high applied f1uo-ride concentration suggests that the oral fluoride res-ervoir responsible fót the elevated baseline fluoridevalues is dorninated by à different reservoir sourcethan during lhe second clearance phase. However, thespecific sources responsible for these elfects cannotpresently be identified from arnongst the possibilitieslisted earlier.

The above results dernonstrate that repeated use ofdentifrices containing Na2FPOj provides sustainedelevated levels of nu€Yride in the mouth between dailybrushings. Furtherrnore, for a short period after eachbrushing, the salivar)' fluoride concentration is rel a-tively high. The growing body of oral f1uoride data

becomes 01' key importance if it can be shown thar l~observed low fluo ride concentrations can maintain 11protective effect against dental caries. This aspecj \\i"

bethesu~ectofasubsequentpaper. •

Ref'erences

Aasenden R, Brudevold F, Richardson 13:Clearance 01' Ouori~~from the mouth after ropical treatment 01' lhe use of a Ouorid.rnouthrinse, Arch Oral 13iol 1968; I3:625-636. .

Birkeland JM: Fluoride content of dental plaque after brushin 'with a fluoride denlifrice. Scand.J Dent Res 1972;80:80-81. !

Bruun C, Givskov H, Thylstrup A: Whole saliva fluoride afttttoothbrusbing with NaF and MFP dentifrices with different rconcentrations, Caries Res 1984:282-288.

Bruun C, Larnbrou D, Larsen MJ, Fejerskov O, Thylstrup A: Fluo.ride in mixed human saliva after different topical fluoride lreai.ments and possible relation to caries inhibition. CommunitDent Oral EpidemioI1982;10:124-129. .

Bruun C, Qvist V, Thylstrup A: Effect of flavour and detergent 00

fluoride availability in whole saliva after use of NaF and MFPdentifrices. Caries Res 1987;21:427-434.

Corpron RE, More FJ, Clark JW: In vivo remineralisation of artifi.cial enamel lesions by a fluoride dentifrice 01' mouthrinse.Caries Res 1986;20:48-55.

Dawes C: Avrnathematical model of salivar)' c1earance of su arIrorn the oral cavity. Caries Res 1983; 17:321-334.

Duckworth RM, Jones S: On the interaction between f1uorine spe.cies and oral soft tissue. J Dent Res I989a;68:560. '

Duckworth RM, Jorres S: On the relationship betwecn salivar\fluoride c1earance and the rate of salivary Ilow, Caries Re's1989b;23:43 7-438. .

Duckworth RM, Morgan SN, Burchell CK: Fluoride in plaque foi. ~lowing use 01' dentifrices containing sodium moncfluorophs.,phate. J Dent Res 1989;68: 130-133,

Duckworth RM, Morgan SN, Murray AM: Fluoride in saliva <Indplaque following use of fluoride-containing mouthwashes. JDent Res 1987;66:1730-1734.

Ekstrand J, Lagerlõf F, Oliveby A: Some aspects of the kinetics off1uoride in saliva; in Leach SA, Edgar WM (eds): Factors Rela].ing to Demineralisation and Remineralisation ofthe Teeth. Ox.ford, IRL Press, 1986, pp 91-98.

Featherstone JDB, O'Reilly MM, Shariati M, Brugler S: Enhanc-.ment of rernineralisation in vitro and ín vivo; in Leach SA, Ed.gar WM (eds): Factors Relating to Demineralísatíon and Re.mineralisation oftheTeeth. Oxford, IRL Press, 1986, pp 23-34.

Fejerskov O, Thylstrup A, Larsen MJ: Rational use of Iluorides incaries prevention. A concept based on possible cariostaticmechanisms. Acta Odontol Scand 1981;39:241-249.

Finidorí C, Lamendin H: Amount of fluorine in saliva after use ofvarious toothpastes. Chir Dent Fr 1980;50:43-48.

Gelhard TBFM, Arends J: Microradiography of in vivo reminera. I

lised lesions in human enamel. J Biol Buccale 1984;12:59-65.Gilbert RJ, Fraser SB, van der Ouderaa FJO: Oral disposition of

triclosan (2,4,4' -trichJoro-2' -hydroxydiphenyl ether) deli veredfrom a dentífrice. Caries Res 1987;21:29-36. 'I;

Gilbert RJ, WilJiams PEO: The oral retention and antiplaque effi.

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Page 7: Oral fluoride retention after uso of fluoride dentifrices

~Iuoride fro_m_D_e_Il_1i_fr_ic_e_s . 12_91.!lI..•

C:lçy 01' triclosan in human volurucers. Br J Clin Pharrnncol!9~7: ~J:5 79-5~U.

G0(lfhuis J, Purdell-Lewis DJ: 0.25% and 0.4% amine fluoride gelI<lrweek ly ropical application. An in vivo study on human den-tal enamel. Cáries Res 1986;20:458-464.

HcintzeU, Petersson LG: Accumulation and clearanee of fluoridein hurnan mixed saliva after different topical fluoride treat-\11cnts.Swed Deru 11979;3:141-148.

Ip~nllnGS, Morgan SN: Oral fluoride lcvels and ambient fluoride. inwke. Cáries Res 1987:21: 179.

J0l"t L:lrscn M. Lambrou 1). Fejcrsk ov O. T<I('h05 B: A study on3ccui11ulati,)n and release of looscly bound fluoridc on cnarnel.earies Res 1981; 15:273-277.

deKloet HJ, Exterkare RAM, Rempt HE. ten Cate JM: In vivo bo-vine enamel rernineralisation and fluoride uptake frorn twodentifrices containing different fluoride concentrations. J DentRes 1936;65:1410-1414.

~{ainW3ring Pl: Fluoride, calciurn and phosphorus concentrations· in pia que following the use of a sodium monofluorophosphate

toothraste (SM FP) containing ca1cium glycerophosphate(CaGP). l I. J Dent Res 1976;55(speeial issue D):142.

\13rquardt DW: An algorithm for least-squares estimation of non-· linear pararneters, J Soe lnd Appl Math 1963: 11 :431-441.Marthaler TM: Explanations for changing patterns of disease in

rhe western world; in Guggenheim B (ed): Cariology Today. Ba-,:1. Karger. 1984. pp 13-23.

\!e!lberg .lR, Castrovince LA, Rotsides ID: ln vivo remineralisa-· tion by a monofluorophcsphate dentifrice as determined with a

tl1in-section sandwieh rnethod. J DeI1l Res 1986;65: I078-1083.\!eIlberg JR. Chornicki WG, Mallon DE, Castrovince LA: Rernin-· erali,ation in vivo of artificial caries lesions by a rnonof1uoro-

phosphate dentifrice. Cáries Res 1985: 19: 126-135.MlIrray JJ, Rugg-Gunn AJ: Fluorides in Cáries Prevention. Bristol,

Wright-PSG,1982Olil'eby A, Lagerlõf F, Ekstrand J, Dawes C: Studies on fluoride

excretion in hi.rnan whole saliva and its relation to flow rate3nd plasma tluoride lcvels. Caries Res 1989;23:243-246.

van der Ouderaa FJG, Cummins D: Delivery systems for agents insupra- and sub-gingival pia que contro!. 1 Dent Res 1989;68

(speci:!I issue): 1617 -1624.

elI,

.11

! I

Renson CE. Crielaers PJA, lbikunlc SAJ, et al: Changing patternsof oral health and implications Ior oral hcalih manpowcr. l. lntDent J 1985;35:235-251.

R611a G: On the role 01" calcium fluoride in the cariostatic mecha-nism offluoride. ACIGlOdontol Scand 1988;46:341·-345.

R6l1a G, 0gaard B: Reduction in caries incidence in Norway from1970 to 1984 and some considerations concerning lhe reason forthis phenomenon: in Frank RM, O'Hickey S (cds): Strategy forDental Cáries Pre 'ention in European Countries According toTheir Laws anel Regulations, Oxford, IRL. Preso, 1987. pp145-·154.

Schâfer F: Evaluarion 01" the aniicaries benefit 01" fluoridc iooth-pastes using an enamel insert model. Caries Res 1989;23:81-86.

Sreebny LM, Chatterjee R, Kleinberg I: Clearance of glueose andsucrose from lhe saliva of human subjects. Arch Oral Biol1985;30:269-274.

Stephen K W, Creanor SL, Russell n, Burchell CK, Huntington E,Downie CFA: A 3-year oral health dose response study of so-diurn monofluorophosphate dentifrices with and without zinccitrate: Anti-caries results. Community Dent Oral Epidemiol1988; 16:321-325.

Wagner JG: Fundamentais of Clinical Pharmacokinetics. Wash-ington, Drug Intelligence Publications, 1975.

Zero DT, Fu J, Espeland MA, Featherstone lDB: Comparison arfluoride concentrations in unstimulared whole saliva followinguse of a fluoride dentifrice and a fluoride rinsc, J Dcnt Rcs1988;67: 1257-1262.

Received: March 19, 1990Accepted after revision: Septernber 15, 1990

R.M. DuckworthUnilever Dental ResearchUnilevcr Research Port Sunlight LaboraroryQuarry Road EastBebingtonWirral, Merseyside L63 3JW (UK)

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Page 8: Oral fluoride retention after uso of fluoride dentifrices

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