Short term serum pharmacokinetics of diammine silver fluoride after oral application

Elsa Vasquez, Graciela Zegarra, Edgar Chirinos, Jorge L Castillo, Donald R Taves, Gene E Watson, Russell Dills, Lloyd L Mancl, Peter Milgrom, Elsa Vasquez, Graciela Zegarra, Edgar Chirinos, Jorge L Castillo, Donald R Taves, Gene E Watson, Russell Dills, Lloyd L Mancl, Peter Milgrom

Abstract

Background: There is growing interest in the use of diammine silver fluoride (DSF) as a topical agent to treat dentin hypersensitivity and dental caries as gauged by increasing published research from many parts of the world. While DSF has been available in various formulations for many years, most of its pharmacokinetic aspects within the therapeutic concentration range have never been fully characterized.

Methods: This preliminary study determined the applied doses (3 teeth treated), maximum serum concentrations, and time to maximum serum concentration for fluoride and silver in 6 adults over 4 h. Fluoride was determined using the indirect diffusion method with a fluoride selective electrode, and silver was determined using inductively coupled plasma-mass spectrometry. The mean amount of DSF solution applied to the 3 teeth was 7.57 mg (6.04 μL).

Results: Over the 4 hour observation period, the mean maximum serum concentrations were 1.86 μmol/L for fluoride and 206 nmol/L for silver. These maximums were reached 3.0 h and 2.5 h for fluoride and silver, respectively.

Conclusions: Fluoride exposure was below the U.S. Environmental Protection Agency (EPA) oral reference dose. Silver exposure exceeded the EPA oral reference dose for cumulative daily exposure over a lifetime, but for occasional use was well below concentrations associated with toxicity. This preliminary study suggests that serum concentrations of fluoride and silver after topical application of DSF should pose little toxicity risk when used in adults.

Clinical trials registration: NCT01664871.

Figures

Figure 1
Figure 1
Mean (±SD) serum fluoride(μmol/L) after topical application of diammine silver fluoride to the facial (buccal) surfaces of 3 teeth in 6 adults.
Figure 2
Figure 2
Silver values (nmol/L) after topical application of diammine silver fluoride to the facial (buccal) surfaces of 3 teeth in 6 adults.

References

    1. Castillo J, Rivera S, Aparicio T, Lazo R, Aw TC, Mancl L, Milgrom P. The short-term effects of diammine silver fluoride on tooth sensitivity: a randomized controlled trial. J Dent Res. 2011;90(2):203–208. doi: 10.1177/0022034510388516.
    1. Ritter AV, Del Dias W, Miguez P, Caplan DJ, Swift EJ Jr. Treating cervical dentin hypersensitivity with fluoride varnish: a randomized clinical study. J Am Dent Assoc. 2006;137:1013–1020.
    1. Tan HP, Lo ECM, Dyson JE, Luo Y, Corbet EF. A randomized trial on root caries prevention in elders. J Den Res. 2010;89(10):1086–1090. doi: 10.1177/0022034510375825.
    1. Rosenblatt A, Stamford TC, Niederman R. Silver diamine fluoride: a caries ”silver-fluoride bullet. J Den Res. 2009;88:116–125. doi: 10.1177/0022034508329406.
    1. Liu BY, Lo EC, Chu CH, Lin HC. Randomized trial on fluorides and sealants for fissure caries prevention. J Dent Res. 2012;91:753–758. doi: 10.1177/0022034512452278.
    1. Gotjamanos T, Ma P. Potential of 4 per cent silver fluoride to induce fluorosis in rats: clinical implications. Aust Dent J. 2000;45:187–192. doi: 10.1111/j.1834-7819.2000.tb00555.x.
    1. Benson HJ. Microbiological applications: Laboratory manual in general microbiology. 8. New York: McGraw Hill; 2002.
    1. Shrestha R, Joshi DR, Gopal J, Piya S. Oligodynamic action of silver, copper and brass on enteric bacteria isolated from water of Kathmandu Valley. Nepal J Sci Technol. 2009;10:189–193.
    1. Thurman RB, Gerba CP. The molecular mechanisms of copper and silver ion disinfection of bacteria Q2 and viruses. Crit Rev Environ Cont. 1988;18:295–315.
    1. Knight GM, McIntyre JM, Craig GG, Mulyani Zilm PS, Gully NJ. Inability to form a biofilm of Streptococcus mutans on silver fluoride- and potassium iodide-treated demineralized dentin. Quintessence Int. 2009;40:155–161.
    1. Thibodeau EA, Handelman SL, Marquis RE. Inhibition and killing of oral bacteria by silver ions generated with low intensity direct current. J Dent Res. 1978;57:922–926. doi: 10.1177/00220345780570091901.
    1. Tanzer J, Thompson A, Milgrom P, Shirtcliff M. Diammino silver fluoride arrestment of caries associated with anti-microbial action. J Dent Res. 2010;89(Spec Iss B):2082.
    1. de Almeida Lde F, Cavalcanti YW, Valenca AM. In vitro antibacterial activity of silver diamine fluoride in different concentrations. Acta Odontol Latinam. 2011;24:127–131.
    1. Chu CH, Mei L, Seneviratne CJ, Lo EC. Effects of silver diamine fluoride on dentine carious lesions induced by Streptococcus mutans and Actinomyces naeslundii biofilms. Int J Paediatr Dent. 2012;22:2–10.
    1. Rees JS. The prevalence of dentine hypersensitivity in general dental practice in the UK. J Clin Periodontol. 2000;27:860–865. doi: 10.1034/j.1600-051x.2000.027011860.x.
    1. Ekstrand J, Koch G, Petersson LG. Plasma fluoride concentration and urinary fluoride excretion in children following application of the fluoride-containing varnish Duraphat. Caries Res. 1980;14:185–189. doi: 10.1159/000260452.
    1. Taves DR. Separation of fluoride by rapid diffusion using hexamethyldisloxane. Talanta. 1968;15:969–974. doi: 10.1016/0039-9140(68)80097-9.
    1. Taves DR. Determination of submicromolar concentrations of fluoride in biological samples. Talanta. 1968;15:1015–1023. doi: 10.1016/0039-9140(68)80109-2.
    1. Martínez-Mier EA, Cury JA, Heilman JR, Katz BP, Levy SM, Li Y, Maguire A, Margineda J, O’Mullane D, Phantumvanit P, Soto-Rojas AE, Stookey GK, Villa A, Wefel JS, Whelton H, Whitford GM, Zero DT, Zhang W, Zohouri V. Development of gold standard ion-selective electrode-based methods for fluoride analysis. Caries Res. 2011;45:3–12. doi: 10.1159/000321657.
    1. Sara R, Wanninen E. Separation and determination of fluoride by diffusion with hexamethyldisiloxane and use of a fluoride-sensitive electrode. Talanta. 1975;22(12):1033–1036. doi: 10.1016/0039-9140(75)80121-4.
    1. Buckley WR. Localized argyria. Arch Dermatol. 1963;88(5):531–539. doi: 10.1001/archderm.1963.01590230039005.
    1. Fisher NM, Marsh E, Lazova R. Scar-localized argyria secondary to silver sulfadizine cream. J Am Acad Dermatol. 2003;49(4):730–732. doi: 10.1067/S0190-9622(02)61574-9.
    1. Mirasattari SM, Hammond RR, Sharpe MD, Leung FY, Young GB. Myoclonic status epilepticus following repeated oral ingestion of colloidal silver. Neurology. 2004;62(8):1408–1410. doi: 10.1212/.
    1. IRIS: U.S. Environmental Protection Agency, Integrated Risk Information System. Fluorine (soluble fluoride) (CASRN 7782-41-4) 1989. . Accessed February 15, 2012.
    1. Lansdown ABG. A pharmacological and toxicological profile of silver as an antimicrobial agent in medical devices. Adv Pharmacol Sci. 2010;910686:16. doi: 10.1155/2010/910686.
    1. ATSDR. Toxicological profile for silver (CAS#:7440-22-4) 1990. = 539&tid = 97. Accessed February 16, 2012.
    1. Wadhera A, Fung M. Systemic argyria associated with ingestion of colloidal silver. Dermatol Online J. 2005;11(1):12.
    1. FDA. Consumer Advisory. Dietary supplements containing silver may cause permanent discoloration of skin and mucous membranes (Argyria) 2009. . Accessed February 16, 2012.
    1. Pl D, Hazelwood KJ. Exposure-related health effects of silver and silver compounds: a review. Ann Occup Hyg. 2005;49(7):575–585. doi: 10.1093/annhyg/mei019.
    1. Gaul LE, Staud AH. Clinical spectroscopy. Seventy cases of generalized argyrosis following organic and colloidal silver medication including a biospectrometric analysis of ten cases. JAMA. 1935;104(16):1387–1390. doi: 10.1001/jama.1935.02760160011004.
    1. Fung MC, Bowen DL. Silver products for medical indications: risk-benefit assessment. J Toxicol Clin Toxicol. 1996;34(1):119–126. doi: 10.3109/15563659609020246.
    1. Nordberg GF, Gerhardsson L. In: Handbook on toxicity of inorganic compounds. SEILER HG, SIGEL HB, editor. Dekker, NY; 1988. Silver; pp. 619–624.
    1. Jensen EJ, Rungby J, Hansen JC, Schmidt E, Pedersen B, Dahl R. Serum concentrations and accumulation of silver in skin during three months treatment with an anti-smoking chewing gum containing silver acetate. Hum Toxicol. 1988;7(6):535–540. doi: 10.1177/096032718800700603.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する