Determination of chlorhexidine retention in different oral sites using matrix-assisted laser desorption/ionization-time of flight mass spectrometry.

OBJECTIVE: The aim of this study was to determine chlorhexidine retention in different oral sites after a one-time 30 s mouth rinsing. DESIGN: Five volunteers were asked to rinse their mouth with 10 ml of 0.2 % chlorhexidine digluconate for 30 s. After rinsing, samples were collected from the interdental area, buccal dental pellicle, anterior labial and posterior buccal mucosa, and saliva with a microbrush at five-time points within 24 h. Retention of chlorhexidine was measured using matrix-assisted laser desorption/ionization-time of flight mass spectrometry with a quantification limit of 15 ng/ml. RESULTS: Chlorhexidine remained in the oral cavity at micrograms per milliliter levels for 11 h after mouth rinsing and was even detected 24 h after application. The results showed a distinct decline of intraoral chlorhexidine levels during the first 6 h after rinsing and it was then retained at low concentrations for at least 24 h. CONCLUSIONS: The dental pellicle and oral mucosa were favorable sites for chlorhexidine retention. The novel method used for chlorhexidine determination offered excellent quantification limits and readily permitted quantification of chlorhexidine.

Washout kinetics of ethanol from the airways following inhalation of ethanol vapors and use of mouthwash.

Introduction: Breath analyzers are commonly used to test for alcohol intoxication, i.e., elevated systemic levels of ethanol, at workplaces and among vehicle drivers. However, local low-dose exposure to ethanol in the mouth or airways may temporarily increase the breath-alcohol concentration (BrAC) without the systemic ethanol level being affected, leading to false positive test results. The aim of this study was to assess the impact of local ethanol exposure on the BrAC.Methods: Eleven healthy adults (six women) were exposed to on average 856 mg/m3 ethanol vapor for 15 min, followed by repeat collection of exhaled breath in Tedlar bags. One hour later, the subjects washed their mouth for 30 s with a typical mouthwash containing 22% ethanol and post-exposure breaths were again collected repeatedly. Negligible systemic uptake of ethanol was confirmed by analysis of blood sampled before, between and after the exposures. Ethanol in breath and blood was analyzed by gas chromatography.Results: No or very low levels (less than 0.002 mg/g) of ethanol were detected in blood at any time point, indicating negligible systemic uptake. The decline in breath was mono-exponential after both exposures with average half times of 0.4 (range 0.3-0.8) min after inhalation exposure and 1.9 (1.1-3.0) min after mouthwash. BrAC levels in the first sample, collected a few seconds after exposure, were 0.14 (0.07-0.13) mg/L after inhalation and 4.4 (2.7-6.0) mg/L after mouth wash. On average, it took 0.5 (0.06-0.7) min and 11 (6-15) min, respectively, for the BrAC to fall below the Swedish statutory limit of 0.1 mg/L air.Conclusion: In practice, use of breath analysis should not be a problem even if the subject inhaled ethanol vapors before the test. In contrast, use of ethanol-containing mouthwash results in a false positive test if sampling is done within 15 min.

A clinical and microbiological study on the enantiomers of delmopinol.

Objective The clinical part of this study aimed to investigate whether the racemate of delmopinol [(±)-delmopinol] is equivalent to its two enantiomers [(+)-delmopinol and (-)-delmopinol] with respect to efficiency and to determine and compare their pharmacokinetic properties. The purpose of the pre-clinical part was to elucidate possible differences in antimicrobial efficiency. Materials and methods The compounds were tested clinically in a double-blind, randomized, cross-over study comprising three treatment periods of 4 days each. The antimicrobial efficacy of the enantiomers was compared in vitro with respect to planktonic and biofilm bacteria of different species. Results No statistically significant differences in prevention of plaque formation were observed. Except for a somewhat higher systemic exposure in terms of AUC and Cmax indicated for (-)-delmopinol compared to (+)-delmopinol, the pharmacokinetic properties were similar. The most common adverse event was a transient anaesthetic feeling in the mouth. This event was reported with the same frequency for all three test solutions. The enantiomers showed similar antimicrobial effects on planktonic bacteria and their biofilms. Conclusions The enantiomers were found to be equally effective with respect to inhibition of plaque development and only minor differences were observed with respect to their pharmacokinetic properties. No differences could be observed in the adverse events reports. There is, therefore, no reason to use one of the enantiomers of delmopinol instead of the racemate. This was further supported by the antimicrobial tests. It is suggested that the combined action of cationic and neutral delmopinol is important for its effect on biofilms.

Can mouth washes containing chlorhexidine 0.12% be used as synonym of a water solution of chlorhexidine 0.12%? / Pode lavagens da boca contendo 0.12 % de clorexidina ser utilizado como sinónimo de uma solução aquosa de cloro-hexidina 0.12 % ?

Chlorhexidine digluconate (CHX) is a gold standard drug in dentistry and is widely used as a reference in both in vitro and in vivoexperiments. Due to ease of access, mouth washes containing CHX 0.12% are used as a substitute for aqueous CHX 0.12% solution in laboratory experiments. Additionally, it is well known that for product flavor purposes, volatile compounds are added to mouth washes formulations. Volatiles added to CHX 0.12% may improve wash's antibacterial ability. Volatiles add potency to the mouth wash formulation. Compared with an aqueous CHX 0.12% solution, it is proposed that CHX solutions and Periogard^® would have antimicrobial activity. Antimicrobial activity was assessed in the present study via disk diffusion assays against Streptococcus mutans, Streptococcus sanguinisand Escherichia coli. Periogard^® showed a significantly higher antibacterial activity in relation to CHX 0.12% (p<0.05) and a similar activity in relation to CHX 1% (p>0.05). Periogard^(r) volatiles were analyzed by gas-chromatography/mass spectrometry (GCMS) and the presence of antibacterial menthol, menthone, isomenthol, menthyl acetate, trans-anethol and eugenol was verified. Finally, the use of Periogard^® as a synonym of CHX 0.12% must be avoided, because its antibacterial activity is closely related to CHX 1%...

Gluconato de clorexidina (CHX) é um fármaco considerado padrão ouro, em Odontologia, amplamente usado como referência em estudos in vitro e in vivo. Em razão da facilidade de acesso, enxaguatórios bucais que contêm CHX 0,12% são usados em substituição à solução aquosa de clorexidina (CHX 0,12%), em experimentos laboratoriais. É sabido que devido à palatabilidade do produto, os mesmos enxaguatórios bucais contêm compostos voláteis em sua formulação, além da CHX 0.12%. Visto que voláteis adicionados podem acrescentar poder antibacteriano à formulação, a comparação da resposta antibacteriana da solução aquosa de CHX em diferentes concentrações e de Periogard^® é proposta no presente artigo. Para tanto, utilizou-se o ensaio do disco de difusão em ágar com inóculos de Streptococcus mutans, Streptococcus sanguinis e Escherichia coli. Periogard^® mostrou atividade antibacteriana significativa contra as três cepas analisadas, quando comparada à atividade de CHX 0.12% (p<0,05) e atividade similar à CHX diluída a 1% (p>0,05). A presença de compostos voláteis no Periogard^® foi analisada por GC-MS e observou-se que mentol, mentona, isomentol, acetato de mentila, trans-anetol e eugenol estão presentes na formulação. Deste modo, o uso de Periogard^(r) como sinônimo de CHX 0,12% deve ser evitado, uma vez que sua atividade se assemelha àquela da CHX diluída a 1%...

On the relationship between the rate of salivary flow and salivary fluoride clearance.

The amount of fluoride retained in the mouth following the application of dentifrices, mouthwashes, etc. may be important in determining their anticaries efficacy. In this study we investigated the relationship between the salivary flow rate and salivary fluoride clearance. Ten adults tested six mouthrinses, consisting of aqueous sodium fluoride solutions (0.013, 0.026 mol/l) with and without added sodium chloride (1.28 mol/l) or sucrose (0.44 mol/l), in a randomised order. Prior to each test, subjects swallowed, rinsed for 2 min with 2 ml water and then expectorated into a preweighed container to obtain a measure of initial saliva flow rate. Next, the procedure was repeated using one of the test rinses. Finally, samples of unstimulated whole saliva were collected for up to 3 h after each mouthrinse application and analysed for fluoride. Salivary fluoride concentrations were significantly lower after application of mouthrinses that contained either sucrose or NaCl, both of which compounds markedly enhanced salivary flow, than after the use of corresponding mouthrinses without any additive. Area under the salivary fluoride clearance curve (AUC) values were inversely correlated with salivary flow rate on an individual basis (p < 0.01). The observed behaviour could not be completely attributed to treatment dilution by saliva at the time of application.

In vitro CPC retention and VSC adsorption by IPM oil droplets: possible mechanisms of action of a two phase mouthwash.

Two phase oil-water mouthwash has been previously shown to efficiently bind oral microorganisms, relying on their cell surface hydrophobicity. The aim of the present in vitro study was to test the cetylpyridinium chloride (CPC) retention and volatile sulfide compounds (VSCs) adsorption abilities of the oil droplets created by mixing of a two phase oil-water solution. VSC adsorption was assayed using a salivary incubation assay and garlic powder solutions, and demonstrated using microscopic sulfide assay. CPC retention was assayed by kinetic and endpoint measurement of Streptococcus salivarius outgrowth using microplate (ELISA) reader. Results showed that the isopropyl myristate (IPM) oil droplets in the two phase solutions were able to adsorb 68-80% of VSCs. CPC at a concentration of 0.05% was most affectively retained by the oil droplets showing a significantly increase in residual antibacterial activity against Streptococcus salivarius. These results taken together, suggests that VSC adsorption and CPC retention by IPM oil droplets may be two additional mechanisms in the activity of the two phase mouthwash formulation.

Absorption of triphenylmethane dyes Brilliant Blue and Patent Blue through intact skin, shaven skin and lingual mucosa from daily life products.

Currently, there is evidence of health risks of triphenylmethane dyes after systemic absorption. This paper investigates the fate of Brilliant Blue (BB) and Patent Blue (PB) after 24-h in vitro diffusion, firstly through intact and secondly through shaven pig-ear skin (stored by freezing) from four leave-on cosmetics under in-use conditions. Both dyes showed no measurable permeation through intact skin but significant permeation was found through shaven skin. From 250 ng/cm(2) of dye in one applied dose there were found 52 ng/cm(2) of BB and 91 ng/cm(2) of PB from ethanol-based after-shave, 39 ng/cm(2) of BB and 86 ng/cm(2) of PB from ethanol-free facial-cleanser, 35 ng/cm(2) of BB and 43 ng/cm(2) of PB from O/W emulsion, and no amount from W/O emulsion, as available to become systemically absorbed. Thirdly, the paper focuses on lingual mucosa after licking lollipops. Ex vivo porcine tongue dorsum was exposed to human saliva with 15,000 ng/cm(2) of dye for 20 min. 24-h diffusion resulted in 34 ng/cm(2) of BB and 86 ng/cm(2) of PB which can be directly absorbed into the blood system. Findings are troubling, particularly with regard to the frequent use of after-shave products by the male population and repeated lollipops licking by children.

Effect of post-brushing mouthwash solutions on salivary fluoride retention--study 2.

OBJECTIVE: This study evaluated the effects of three post-brushing mouthwashes containing 0 ppm F, 225 ppm F, and 500 ppm F, respectively, on salivary fluoride retention after brushing with 1450 ppm fluoride (as NaF) toothpaste and rinsing with water immediately after brushing. METHODS: In this three-phase, randomized, cross-over study, an ion-specific electrode was used to measure salivary F levels in thirty trial participants before brushing (Time 0), and after brushing, rinsing with water, and then rinsing with one of the three mouthwashes. Time points evaluated after brushing were one, three, five, 10, 20, 30, 45, and 60 minutes. For saliva sample collections, subjects were asked to pool saliva in their mouths for 10 seconds before spitting out into a container for each of the time points. RESULTS: The AUC0-60 means for F in saliva were 554, 252, and 20 for the 500, 225, and 0 ppm F mouthwash groups, respectively. The 500 ppm F mouthwash resulted in a 2660% increase in total fluoride salivary retention over 60 minutes when compared with the 0 ppm F group, and a 120% increase when compared with the 225 ppm F group. A significant difference (p < 0.001) in the AUC0-60 means between the three groups was observed using analysis of variance (ANOVA). Paired t-tests also showed significant differences in the mean fluoride retention over 60 minutes for all three pair-wise group comparisons (p < 0.001). CONCLUSION: Use of a fluoride mouthwash containing 225 ppm F or 500 ppm F produced a significant increase in salivary fluoride retention following brushing with a 1450 ppm F toothpaste and rinsing with water compared to rinsing without fluoride. The use of the 500 ppm F mouthwash may be of particular benefit to those at high caries risk.

Retention of KOH-soluble fluoride formed after application of a SnCl(2)/AmF/NaF containing mouth rinse under erosive conditions.

OBJECTIVE: Application of SnCl(2)/AmF/NaF containing mouth rinse showed good protection against erosion. The aim of the study was to evaluate if this is due to the amount of KOH-soluble fluoride (KOHsF) formed or its resistance under erosive conditions. METHODS: One hundred and fifty bovine enamel samples were allocated to five groups (n = 30) and were once eroded in 0.05 mol/l citric acid (5 min). Samples were stored in artificial saliva for 4 days. Samples of two groups (erosive-SnCl(2) + erosive-NaF) were eroded 6 × for 5 min. The remaining samples were stored in aqua dest deionised water. Each day the samples were treated twice for 2 min with 1 ml SnCl(2)/AmF/NaF-solution (erosive-SnCl(2);neutral-SnCl(2)/AmF/NaF) or NaF-solution (erosive-NaF;neutral-NaF). The fifth group remained untreated (control). On day 5, 10 samples of each group were used for determination of KOHsF (series 1). The remaining samples were again eroded (erosive-SnCl(2) + erosive-NaF) or stored in artificial saliva (neutral-SnCl(2) + neutral-NaF). KOHsF of another 10 samples of each group was measured (series 2). The last 10 samples of each group were also treated as described above and the amount of KOHsF was measured (series 3). RESULTS: In each series 1-3 KOHsF in group erosive-SnCl(2)/AmF/NaF were significantly higher. No significant loss of KOHsF between the series 1-3 was observed (except for control). CONCLUSION: SnCl(2)/AmF/NaF containing mouth rinse revealed a better formation of KOH-soluble fluoride as the NaF-solution, although the applied fluoride compound has no influence on the stability of the KOHsF under erosive conditions, leading to the conclusion that the resistance of KOHsF is not responsible for the difference in the protection against dental erosion.

Anticaries potential of commercial fluoride rinses as determined by fluoridation and remineralization efficiency.

OBJECTIVE: The objective of this work was to compare the anticaries potential of several currently marketed fluoride-containing mouthrinse products using two in vitro approaches: 1) fluoride uptake studies of demineralized human enamel samples after exposure to rinse products; and 2) microhardness studies of sound enamel samples after exposure to the rinse products and demineralizing agents. METHODS: Four currently marketed rinse products, formulated at 100 ppm F, were evaluated in fluoride uptake studies relative to a negative (water) rinse control (Study 1). The same rinse products were evaluated in microhardness studies (Study 2) against a positive control, ACT Anticavity rinse, which is formulated with 225 ppm F and carries the ADA Seal of Acceptance as an effective anticavity mouthrinse. Test products included ACT Total Care rinse (pH = 6.34), Listerine Total Care rinse (pH = 3.57), Crest Pro-Health for Me rinse (pH = 3.33), and Crest Pro-Health Complete rinse (pH = 3.43). RESULTS: Study 1-Samples treated with any of the fluoride-containing rinses showed significantly higher (p < 0.05) levels of fluoride uptake than the negative (water) control. Two of the products (Crest Pro-Health for Me and Crest Pro-Health Complete) showed significantly higher (p < 0.05) levels of fluoride uptake into demineralized enamel than the other marketed rinses (Listerine Total Care and ACT Total Care). Study 2-Samples treated with the same two rinse products (Crest Pro-Health For Me and Crest Pro-Health Complete) showed significantly lower mineral loss than the other rinse products, as well as the positive control. CONCLUSION: Results of these in vitro studies indicate that the Crest mouthrinse products evaluated here are capable of providing significantly better fluoridation of demineralized enamel, as well as significantly better protection against the initiation and progression of demineralization, compared to the other marketed fluoride-containing mouthrinse products tested.

Acute and substantive action of antimicrobial toothpastes and mouthrinses on oral biofilm in vitro.

The aim of this study was to compare acute action by killing or disrupting oral biofilms through the use of antimicrobial toothpastes and mouthrinses in vitro and to investigate substantive action by absorption of antimicrobials in a biofilm. Biofilms from freshly collected human saliva were grown in 96-well microtitre plates. After removal of saliva, the wells of the microtitre plates were washed with sterile water (control), or exposed to a dilution series of mouthrinses (Corsodyl, Listerine, Meridol, Crest Pro Health) or to toothpaste slurries (Prodent Coolmint, Colgate Total, Zendium Classic, Crest Pro Health, Oral B Pro Expert, Crest Cavity Protection). Acute action was concluded from reduced continued (16 h) growth of treated biofilms with respect to the control. Substantive action was studied by exposing dead biofilms to mouthrinses or to toothpaste slurry. Substantive action through the absorption and subsequent release of antimicrobials from biofilm was concluded from reduced growth on top of the treated biofilms. All formulations showed acute action at the highest concentrations studied. Further dilution yielded loss of efficacy, or even stimulation of biofilm growth. Antimicrobial absorption in and the release of effective concentrations of antimicrobials from dead biofilms, was demonstrated for three selected antimicrobial products, indicating that antimicrobials remain bio-available for substantive action on new biofilms.

A nonstaining and tasteless hydrophobic salt of chlorhexidine.

Chlorhexidine (CHX) remains one of the most effective and widely used antiplaque agents around the world, although its side effects still limit a long-term usage as the patient compliance for oral treatment with CHX. We hypothesize that a less water-soluble tetracation salt of CHX might be able to interact weakly with tooth enamel and oral taste cells, reducing those undesirable side effects of CHX. The chlorhexidine tetrapalmitate (CHXTP) was obtained and the antimicrobial activity was evaluated by hole-plate diffusion method and twofold tube dilution method; for measurement of its propensity to stain, we used the in vitro method of polymethylmethacrylate blocks in an infusion with black tea solution; the rate of its removal from oral cavity was studied by high-performance liquid chromatography measurement of CHX extracted from human saliva samples; and its effect on the human taste perception was evaluated by taste confusion matrix method. The results showed that CHXTP salt is very active against Streptococcus mutans, with no interference on taste perception and a low tendency to stain; however, chlorhexidine digluconate shows a better retention in saliva. The use of polyvinylpyrrolidone turned possible a nonstaining and tasteless CHXTP formulation to linger in mouth.

Pharmacokinetics and clinical efficacy of delmopinol in an open rinse time study in healthy volunteers.

PURPOSE: To compare three different rinse times with delmopinol (15, 30 and 60 seconds) with respect to inhibition of plaque growth and to determine the pharmacokinetic parameters of delmopinol for these rinse times. METHODS: This open and randomized study with a cross-over design was performed in healthy male volunteers and consisted of four treatment periods of 1 week separated by washout periods of at least 6 days. The first test period started with staining of the teeth followed by planimetric recordings before and after professional cleaning. Adverse records were also obtained. The volunteers, randomly assigned to a rinsing time sequence, were instructed to cease all oral hygiene measures except for the mouthrinse with placebo or delmopinol solutions. The rinses were performed without supervision twice daily for 7 days for each rinsing time. On Day 7, plaque % index and planimetric registrations were obtained, adverse effects recorded and the teeth were cleaned professionally. Plasma samples for the pharmacokinetic evaluation were also taken. The remaining test periods were performed in the same way, except that no baseline planimetric recordings were made. During the washout periods the volunteers returned to their normal oral hygiene behavior. Venous blood samples were drawn from all volunteers into sodium heparin-containing tubes. RESULTS: A significant time-response was obtained with respect to the planimetric results. The mean areas of the teeth covered with plaque after the test periods (placebo, 15, 30 and 60 seconds) were 41%, 29%, 23% and 18%, respectively. Statistical analysis showed that rinsing with delmopinol for 30 or 60 seconds differed significantly (P < 0.05) from placebo. There was also a significant difference between rinsing for 15 and 60 seconds. From the plaque % index data it was found that all three rinsing times differed significantly from placebo. However, between the three rinse times with active solution, no significant difference in plaque % index occurred. Statistical analysis of the systemic exposure, in terms of the pharmacokinetic parameters AUC(12h) and C(max) showed a significant treatment effect. The exposure increased with increasing rinse time, although the increase (AUC(12h) and C(max)) was less than proportional to the rinse time.

AG013, a mouth rinse formulation of Lactococcus lactis secreting human Trefoil Factor 1, provides a safe and efficacious therapeutic tool for treating oral mucositis.

Non-clinical studies, focusing on the pharmacodynamics (PD), pharmacokinetics (PK) and safety pharmacology of genetically modified Lactococcus lactis (L. lactis) bacteria, engineered to secrete human Trefoil Factor 1 (hTFF1), were performed to provide proof-of-concept for the treatment of oral mucositis (OM) patients. L. lactis strain sAGX0085 was constructed by stably inserting an htff1 expression cassette into the bacterial genome, and clinically formulated as a mouth rinse (coded AG013). PD studies, using different oral dosing regimens, were performed in a clinically relevant hamster model for radiation-induced OM. The PK profile was assessed in healthy hamsters and in hamsters with radiation-induced OM. In addition, in vitro and in vivo safety pharmacology studies were conducted, in pooled, complement-preserved human serum, and in neutropenic hamsters and rats respectively. Topical administration of L. lactis sAGX0085/AG013 to the oral mucosa significantly reduced the severity and course of radiation-induced OM. PK studies demonstrated that both living L. lactis bacteria, as well as the hTFF1 secreted, could be recovered from the administration site for maximum 24h post-dosing, without systemic exposure. The in vitro and in vivo safety pharmacology studies confirmed that L. lactis sAGX0085 could not survive in systemic circulation, not even under neutropenic conditions. The results from the PD, PK and safety pharmacology studies reported here indicate that in situ secretion of hTFF1 by topically administered L. lactis bacteria provides a safe and efficacious therapeutic tool for the prevention and treatment of OM.

Evaluation of salivary fluoride retention from a new high fluoride mouthrinse.

OBJECTIVES: To evaluate salivary fluoride retention from a new high fluoride daily use mouthrinse over a 120 min period. METHODS: Sixteen subjects completed a randomised single-blind, four-treatment cross-over trial. Sensodyne® Pronamel® mouthrinse (A) contained 450 ppm fluoride; reference products were Colgate® Fluorigard® (B), Listerine® Total Care (C) and Listerine Softmint Sensation (D) containing 225, 100 and 0 ppm fluoride respectively. Salivary fluoride retention was monitored ex vivo after a single supervised use of test product (10 mL, 60 s). Samples were collected at 0, 1, 3, 5, 15, 30, 60 and 120 min post-rinse, generating fluoride clearance curves from which the area under the curve (AUC) was calculated. Differences in salivary fluoride concentrations for each product were analysed using ANCOVA at each time point using a 5% significance level, as well as lnAUC for the periods 0-120, 0-1, 1-15, 15-60 and 60-120 min. Pairwise comparisons between all treatment groups were performed. RESULTS: Salivary fluoride levels for A-C peaked immediately following use. Fluoride levels were statistically significantly higher for A versus B-D (p≤ 0.004), linear dose responses were apparent. AUC(0-120) was statistically significantly greater for A than for B (p = 0.035), C (p< 0.0001) and D (p< 0.0001). Post-hoc comparisons of lnAUC for the remaining time domains showed fluoride retention from A was statistically significantly greater versus B-D (p< 0.0001). CONCLUSIONS: Single-use treatment with the new mouthrinse containing 450 ppm fluoride resulted in statistically significantly higher salivary fluoride levels throughout the 120 min test period. Total fluoride retention (AUC(0-120)) was also statistically significantly greater versus comparator rinse treatments.

Investigation of triclosan retention and dental plaque viability with a triclosan/PVM/MA copolymer mouthrinse in a Thai population.

This investigation studied triclosan retention and plaque viability in a group of healthy human subjects from Bangkok, Thailand, 12 hours after using a mouthrinse containing a triclosan/PVM/MA copolymer system. The results show the retained triclosan in the dental plaque was with in or higher than the minimum inhibitory concentration (MIC range 0.27-6.25 microg/ml), indicating the triclosan in this product remains at an effective concentration in dental plaque. The 12-hour post-application evaluation demonstrated only 36.5% viability of oral bacteria in dental plaque after a one-time use of the mouthrinse. This study shows the benefits of using a mouthrinse containing a triclosan/PVM/MA copolymer system for providing 12 hours long-lasting anti-bacteria and dental plaque control.

Pharmacokinetics and pharmacodynamic action of budesonide after buccal administration in healthy subjects and patients with oral chronic graft-versus-host disease.

Buccal administration of budesonide (mouthwash) may be effective as a topical add-on therapy in patients with oral chronic graft-versus-host disease (cGVHD). Safety of approved oral budesonide is based on high intestinal and hepatic extraction by cytochrome P450 3A (CYP3A) enzymes. The purpose of this study was to evaluate the presystemic extraction and pharmacodynamic action of buccal budesonide. Oral budesonide (3 mg) was taken as reference to which various single and multiple dose regimens of buccal budesonide were compared. Budesonide and the 2 main CYP3A-dependent metabolites (6beta-hydroxybudesonide, 16alpha-hydroxyprednisolone) were analyzed in blood and urine along with the drug's effect on endogenous cortisol in 12 healthy subjects and 7 patients with oral cGVHD. We assessed CYP3A-dependent metabolites in both healthy subjects and patients after buccal budesonide. Whereas systemic exposure to budesonide was markedly lower in healthy subjects after the mouthwash compared to oral dosing (mean relative bioavailability 18%-36%), the systemic concentrations thereafter in patients were as high as those after the identical dose of oral budesonide. Reduced buccal CYP3A activity (lower inactivation of budesonide) in patients contributed to this remarkable difference. Endogenous cortisol was suppressed in some patients during 1 week of continuous treatment with buccal budesonide (3 x 3 mg per day). We are the first to report the biotransformation of budesonide via CYP3A enzymes after buccal drug administration. Only 2% of a buccal dose of budesonide achieves systemic circulation in healthy individuals; that fraction is 10% in patients with oral cGVHD, probably because of alterations in drug uptake and metabolization.

Fluoride concentrations in dental plaque and saliva after the use of a fluoride dentifrice preceded by a calcium lactate rinse.

Plaque fluoride concentrations ([F]) are directly related to plaque calcium concentrations [Ca]. Attempts to increase plaque F uptake from dentifrices or rinses have used methods designed to increase plaque [Ca] but with inconsistent results. This double-blind, double-crossover study tested the effect of a 150 mM calcium lactate rinse used prior to brushing with placebo or fluoridated dentifrices (1030 p.p.m. as NaF) on plaque and salivary [F] and [Ca]. Sixteen children (8-10 yr of age) were randomly assigned to four different groups according to the four treatments (placebo dentifrice or fluoridated dentifrice preceded by calcium lactate or deionized water prerinses). Plaque and saliva were collected 1 and 12 h after brushing on day 7 after starting to use the dentifrices. F was determined using the electrode and Ca was determined using atomic absorption spectrometry. Plaque and salivary [Ca] were not significantly increased after use of the calcium lactate prerinse, except for plaque [Ca] 1 h after the use of the placebo dentifrice. A significant increase in salivary [F] was associated with the calcium lactate prerinse only at 1 h after the use of the fluoridated dentifrice. The the calcium lactate prerinse did not significantly affect plaque [F] under any condition.

The effect of the use of mouthwash on ethylglucuronide concentrations in urine.

Two studies were performed to evaluate the effect of alcohol containing mouthwash on the appearance of ethyl glucuronide (EtG) in urine. In the first study, 9 volunteers were given a 4-oz bottle of mouthwash, which contained 12% ethanol. They gargled with all 4 oz. of the mouthwash at intervals over a 15-min period. All urine samples were collected over the next 24 h. Of 39 provided urine samples, there were 20 > 50 ng/mL, 12 > 100 ng/mL, 5 > 200 ng/mL, 3 > 250 ng/mL, and 1 > 300 ng/mL. The peak concentrations were all within 12 h after the exposure. In the second study, 11 participants gargled 3 times daily for 5 days. The first morning void was collected. Sixteen of the 55 submitted samples contained EtG concentrations of greater than 50 ng/mL. All of them were less than 120 ng/mL. These studies show that incidental exposure to mouthwash containing 12% ethanol, when gargling according to the manufacturer's instructions, can result in urinary EtG values greater than 50 ng/mL. All specimens were negative for ethanol. The limits of detection and quantitation for the EtG testing were 50 ng/mL.