Summary
The doses of fluoride (F) recommended in the literature for caries prevention and for the treatment of osteoporosis vary. This partly reflects inadequate knowledge of F pharmacokinetics. In the present study various single and multiple oral doses of F were given to eight volunteers, who had a strictly controlled F intake in the diet. The resulting plasma and parotid saliva concentrations as well as urinary output of F were measured. The plasma data fitted a two-compartment open model with a β-slope half-life ranging between 2 and 9 h. Plasma clearance was 0.15±0.02 (SD) liter/kg/h. Data from the highest dose (10 mg) were fitted to both two- and three-compartment models, and there was no significant difference between them. Multiple doses of F 3.0 or 4.5 mg yielded steady state concentrations ranging from 54 to 145 ng/ml. About 50 per cent of the given dose was recovered in the urine, which is indicative of considerable accumulation in the body. The saliva F/plasma F concentration ratio was 0.64 with a coefficient of variation of 5%.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adler, P.: Fluorides and dental health. In: Fluorides and Human Health, pp. 323–354. W. H. O. Monograph Series No. 59, Geneva (1970)
Armstrong, W. D., Gedalia, I., Singer, L., Weatherell, I. A., Weidman, S. M.: Distribution of fluorides. In: Fluorides and Human Health, pp. 93–139. W. H. O. Monograph Series No. 59, Geneva (1970)
Boxenbaum, G., Riegelman, S., Elashoff, R. M.: Statistical estimations in pharmacokinetics. J. Pharmacokinet. Biopharm.2, 123–148 (1974)
Dambacher, M. A., Haas, H. G.: Therapie der Osteoporose mit Fluoride. Dtsch. Med. Wschr.101, 504–505 (1976)
Ekstrand, J.: A micromethod for determination of fluoride in blood plasma and saliva. Calcif. Tissue Res.23, 225–228 (1977)
Ekstrand, J., Ehrnebo, M., Boréus, L.: Determination of fluoride bioavailability in man following intravenous and oral administration: The importance of renal clearance and urinary flow. Clin. Pharmacol. Ther. In Press (1977)
Ekstrand, J., Ericsson, Y., Rosell, S.: Absence of protein-bound fluoride from human blood plasma. Arch. Oral Biol.22, 229–232 (1977)
Ericsson, Y., Gydell, K., Hammarskiöld, Th.: Blood plasma fluoride: An indicator of skeletal fluoride content. Int. Res. Commun. Syst.1, 33 (1973)
Forrester, D. J., Schultz, E. M., Jr.: International workshop on fluorides and dental caries reduction. Report, University of Maryland, Baltimore, U. S. A., pp. 25–70 (1974)
Franke, J., Rempel, H., Franke, M.: Three years experience with sodium-fluoride therapy of osteoporosis. Acta orthop. scand.45, 1–20 (1974)
Gibaldi, M., Nagashima, R., Levy, G.: Relationship between drug concentration in plasma or serum and amount of drug in the body. J. Pharm. Sci.58, 193–197 (1969)
Henschler, D., Büttner, W., Patz, J.: Absorption distribution in body fluids and bioavailability of fluoride. In: Calcium Metabolism, Bone and Metabolic Bone Diseases. (eds. Kuhlencordt, F. and Kruse, H. P.) pp. 111–121. Berlin, Heidelberg, New York: Springer 1975
Jowsey, J., Riggs, B. L., Kelly, P. J.: Long-term experience with fluoride and fluoride combination treatment of osteoporosis. In: Calcium Metabolism, Bone and Metabolic Bone Diseases. (eds. Kuhlencordt, F. and Kruse, H. P.) pp. 151–154. Berlin, Heidelberg, New York: Springer 1975
Parkins, F. M., Tinanoff, N., Moutinho, M., Anstey, M. B., Waziri, M. H.: Relationships of human plasma fluoride and bone fluoride to age. Calcif. Tissue Res.16, 335–338 (1974)
Wagner, J. G., Northam, J. I., Alway, C. D., Carpenter, O. S.: Blood levels of drug at the equilibrium state after multiple dosing. Nature207, 1301–1302 (1965)
Weatherell, J. A., Deutsch, D., Robinson, D.: Fluoride and its relation to bone and tooth. In: Calcium Metabolism, Bone and Metabolic Bone Diseases. (eds. Kuhlencordt, F. and Kruse, H. P.) pp. 101–110. Berlin, Heidelberg, New York: Springer 1975
Whitford, G., Pashley, D. H., Stringer, G. I.: Fluoride renal clearance: A pH dependent event. Am. J. Physiol.230, 527–532 (1976)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ekstrand, J., Alván, G., Boréus, L.O. et al. Pharmacokinetics of fluoride in man after single and multiple oral doses. Eur J Clin Pharmacol 12, 311–317 (1977). https://doi.org/10.1007/BF00607432
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00607432