Pharmacokinetics of fluoride in man after single and multiple oral doses

Abstract

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 beta-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%.

Fluoride Pharmacokinetics in Infancy

“…in at least some of the infants, peak plasma concentration had not been reached by 30 min after administration of the supplement. By contrast, in studies of adults (28), peak plasma concentration was regularly achieved by 30 min after administration of the supplement. The longer time required to reach peak plasma concentration by the infants than by the adults may merely reflect the longer period of fasting by the adult subjects (12 h before and 3 h after the time of administration of the supplement).…”

“…Net fractional renal clearance decreased significantly ( r = Although plasma concentrations of fluoride, renal clcarance of fluoride, and fluoride pharmacokinetics have been extensively studied in human adults (27)(28)(29)(30)(31)(32)(33) and renal clearance of fluoride has been studied in children and adolescents (34). the data reported here arc the first concerning infants.…”

“…the area under the plasma concentration curve in a specified subject was greater when the fluoride dose was greater, but between subjects at the same fluoride intake. there was considerable variability in the area under the plasma concentration curve (27,28).…”

Influence of Fluoridated Salt on Urinary Fluoride Excretion of Adults

“…Calculation of the mean value of the additional daily fluoride excretion observed in the three follow-up examinations revealed that by intake of a main meal which is prepared with fluoridated salt this was increased by 0.04 mg/24 h. It has been reported that in adults on average 50-60% of the ingested fluoride is excreted via urine [Ekstrand et al, 1977;Einwag and Trautner, 1984]. Taking into account this assumption the mean increase in fluoride uptake achieved by this measure was 0.07-0.08 mg/24 h. One of the reasons that fluoride excretion of the test group was not increased more distinctly is the habit widespread in Germany not to add spices and salt to meals at table.…”

Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies (NDA) on a request from the Commission related to the Tolerable Upper Intake Level of Fluoride

“…Apart from the intake via water and diet the fluoride concentration in saliva and dental plaque is dependent on topical fluoride application via dental care products (Oliveby et al, 1990;Ekstrand, 1997;Ekstrand, 1977;Ekstrand et al, 1977;Featherstone, 1999;Hetzer, 1997;Sjögren et al, 1993;Twetman et al, 1998). Children with no caries experience were found to have higher salivary fluoride concentrations than children highly affected by caries (40 versus 20 μg/L) (Shields et al, 1987).…”