The Nonlinear Tissue-Binding Character of Fluoride Kinetics in Normal and Anephric Subjects

Kekki, M; Lampainen, E; Kauranen, P.; Hoikka, Veijo; Alhava, Eeva; Pasternack, Amos

doi:10.1159/000182631

Cited by 7 publications

(2 citation statements)

References 2 publications

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“…This was also confirmed in a recent study by . It was suggested by Kekki et al (1982) that the non-linear component might be associated with the first phase of fluoride uptake in bone, before this is incorporated into mineral, after which any exchange is slow. For six months, Richards et al .…”

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confidence: 99%

Pharmacokinetics of Fluoride in Man and its Clinical Relevance

Ekstrand

Vogel

1990

J Dent Res

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A large number of parameters will influence and mediate the activity and the pharmacological response of dental fluoride products after systemic or topical treatment. This report reviews some aspects of the pharmacokinetics of fluoride in man, fluoride bio-availability, plasma kinetics, and kinetics of fluoride in saliva and plaque fluid. Pharmacokinetic studies in growing dogs show that 90% of a single injected fluoride dose is retained shortly after birth, but at maturity it decreases to about 50%. The degree of fluoride accumulating in calcifying tissues seems to be strongly related to age. The bio-availability of fluoride from swallowed fluoride toothpaste is shown to be decreased if the toothpaste is ingested close to a meal. Several studies show that fluoride exerts its cariostatic effects through the liquid phase surrounding the enamel. The importance of fluoride in the fluid environment of the teeth and the kinetics of fluoride in saliva are discussed. Clinical studies using different slow-release fluoride systems indicate that they are promising cariostatic agents--in particular intra-oral slow-release devices and lozenges. A new micro-analytical method to study the kinetics of fluoride in plaque fluid collected from single tooth sites has been developed. Preliminary studies show that the clearance of fluoride from plaque fluid is slowest in the upper incisor region, followed by the molar region, and faster in the lower incisor region. A site-by-site study of the concentration of fluoride in plaque fluid after topical fluoride administration could be extremely beneficial in optimization of the methods and recommended safety regimens for fluoride therapy.

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confidence: 99%

Pharmacokinetics of Fluoride in Man and its Clinical Relevance

Ekstrand

Vogel

1990

J Dent Res

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“…It has been suggested that the nonlinear component may be associated with the first phase of fluoride uptake in bone. (23) Our studies indicate that the kinetics of the plasma profile would be critical to the capacity of the bone to accumulate fluoride. Hence, a dosage regimen that produces more sustained and prolonged plasma levels, in contrast to the high plasma peaks usually seen after intake of plain NaF tablets, might result in a higher degree of fluoride uptake in the bone.…”

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confidence: 76%

Journal of Bone and Mineral Research

Ekstrand

Carl-Johan

1990

Journal of Bone and Mineral Research

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This report reviews some aspects of fluoride pharmacokinetics in relation to the treatment of osteoporosis. The bioavailability of conventional plain NaF tablets has been shown to be close to 100, for sustained-release NaF tablets close to 90%, and for enteric-coated NaF tablets 65%. The simultaneous intake of food and/or calcium tablets reduces the bioavailability by 30 to 40%. Fluoride renal clearance is influenced by both urinary pH and flow and the clinical consequences of this is discussed. Studies on plasma kinetics of fluoride during chronic fluoride intake suggests that a plasma sample taken at mid-dosage intervals will give reproducible "mean steady-state" levels. It is suggested that improvements of the clinical benefit of fluoride therapy in osteoporosis might be achieved if the dosage regimen were based on the pharmacokinetic properties of the fluoride preparation used as well as plasma fluoride monitoring.

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A mathematical model for fluoride uptake by the skeleton

1993

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A mathematical model was developed that predicts fluoride accumulation and clearance from the skeleton based upon fluoride bioavailability, bone remodeling rate, and the fluoride binding characteristics of bone. It was assumed that fluoride binds to bone in a nonlinear fashion such that a smaller percentage of fluoride is bound to bone if fluoride intake is increased to high levels. Bone resorption rate was assumed to be proportional to the solubility of hydroxyfluoroapatite which is inversely related to bone fluoride content. The predictions made by the model compared favorably with experimental results from fluoride uptake and clearance studies. Parametric studies done using the model showed the following: (1) fluoride can be cleared from the skeleton by bone remodeling, but fluoride clearance takes over four times longer than does fluoride uptake; and (2) fluoride uptake by the skeleton was positively associated with bone remodeling rate. However, the concentration of fluoride in newly formed bone does not decrease with reduced remodeling rates and surpasses 10,000 ppm for intakes of fluoride greater than 9 mg/day. For osteoporosis, daily dose and duration of fluoride treatment should be selected to avoid reaching a toxic cumulative bone fluoride content.

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The Nonlinear Tissue-Binding Character of Fluoride Kinetics in Normal and Anephric Subjects

Cited by 7 publications

References 2 publications

Pharmacokinetics of Fluoride in Man and its Clinical Relevance

Pharmacokinetics of Fluoride in Man and its Clinical Relevance

Journal of Bone and Mineral Research

A mathematical model for fluoride uptake by the skeleton

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