Fluoride Pharmacokinetics in Infancy

Abstract

ABSTRACT. Fluoride pharmacokinetic data are presented for infants given a fluoride supplement. Seventeen infants participated in a total of 20 studies. On one day, 0.013 mmol(0.25 mg) fluoride was given as a supplement (fluoride supplement study), and on another day a placebo was given (control study). Samples of plasma and urine were collected for 5 h and analyzed for fluoride. During control studies fluoride intake averaged 0.15 pmol/kg (2.9 pg/kg), and plasma fluoride concentrations ranged from 0.05 to 0.11 pmol/L (10 to 20 pg/L). In nine instances, the quantity of fluoride excreted in the urine was more than twice that consumed. When the fluoride supplement was given, total fluoride intake averaged 1.93 pmol/kg (36.6 pg/kg). Plasma peak concentration was reached by 30 min in 14 studies and by 60 min in six studies. Mean plasma peak fluoride concentration was 3.3 pmollL (63 ng/mL). Area under the plasma concentration curve averaged 236 nmol. m-' . min (4479 ng . mL-' . min) and was not related to the dose of fluoride. The rate of urinary excretion was significantly correlated with rate of urinary flow. When the dose of fluoride was expressed per unit of body weight, fluoride retention was strongly related to the dose. Retention of the fluoride absorbed from the fluoride dose ranged from 75.4 to 87.6%. Plasma clearance averaged 6.8 mL. kg-'. min-' and decreased significantly with age. Net fractional clearance (renal clearance of the fluoride dose/GFR) averaged 56.770, which was significantly greater than the 29% observed during the control studies. The greater percentage retention of fluoride by infants than by adults is probably explained by a greater capacity of the infant to deposit fluoride in hard tissues. (Pediarr Res 35: 157-163, 1994) On the basis of the belief that an adequate intake of fluoride in early life is protective against caries in later life, fluoride supplements are recommended for infants and children living in areas in which the fluoride content of the drinking water is low. However, critical reviews of the evidence (1-3) have led to the conclusion that the effect of fluoride in decreasing the prevalence and severity of dental caries is not primarily systemic but is exerted locally within the oral cavity (4). Because fluoride supplements are quickly cleared from the mouth, the ~ossibilitv must be considered that they may contribute to enamei fluorosis, which is unquestionably a systemic effect, while providing rela-13). As reviewed by Szpunar and Burt (2) and Fomon and Ekstrand (3), little question exists that regular consumption of fluoride supplements increases the risk of enamel fluorosis. However, the relative importance of fluoride supplements and other sources of fluoride intake is unknown.Although metabolic and pharmacokinetic studies of fluoride throughout infancy and childhood are needed. we have focused our attention on studies of infants. Epidemiologic data provide evidence that, at least under some conditions, fluoride intake during infancy may be a causative factor in the ...

Determination of Fluoride Intake from Urinary Fluoride Excretion Data in Children Drinking Fluoridated School Milk

“…The bioavailability of fluoride is reduced when administered with milk and/or other dietary components, with only about 85-90% of the ingested dose being absorbed [Ekstrand and Ehrnebo, 1979;Ekstrand et al, 1984Ekstrand et al, , 1994aTrautner, 1989;Trautner and Einwag, 1989]. Furthermore, the bioavailability of fluoride administered as one single bolus dose is different from that of normal fluoride intake of the same magnitude but divided up throughout the course of a day.…”

Fractional Urinary Fluoride Excretion of Young Female Adults during the Diurnal and Nocturnal Periods

“…Accepting that approximately 10% of the fluoride intake is not absorbed, the daily fluoride retention can be preliminarily estimated as 20% of the ingested fluoride. Copyright © 2008 S. Karger AG, Basel Over recent decades, several studies have been published on the proportion of ingested fluoride that is excreted in the urine [fractional urinary fluoride excretion (FUFE)] in young children [Ekstrand et al, 1984[Ekstrand et al, , 1994aVilla et al, 1999Villa et al, , 2000 Lennon, 2000, 2001;Zohouri and Rugg-Gunn, 2000;Haftenberger et al, 2001;Franco et al, 2005]. On the other hand, studies on FUFE in adults, under usual fluoride intake conditions, are very scarce.…”

Pharmacokinetics of Fluoride in Toddlers After Application of 5% Sodium Fluoride Dental Varnish

“…Mean plasma fluoride concentration was estimated by the total recovered urine fluoride divided by time between diapers, weight of the participant, and the expected renal clearance of fluoride. 21,22 This formula is a rearrangement of the calculation for plasma clearance. Expected renal clearance was taken as the average net plasma fluoride clearance measured during the 5 hours after feeding of a 0.25-mg fluoride supplement to 17 children 3 to 13 months of age (1.09 mL kg 21 min…”

“…Plasma levels are estimated from urinary fluoride collected in each diaper from the same toddler (participant F) on treatment and control days, using the relationship between urine and plasma fluoride in 17 toddlers measured by Ekstrand and colleagues. 21 Plasma fluoride is estimated from total urine fluoride to a mean of 21 mg/L (range, 9.4 to 30 mg/L) after application of fluoride varnish and 13 mg/L (range, 2.8 to 27 mg/L) during the control visit. 22 One child urinated often enough both days to enable plotting of estimated plasma fluoride levels across time (Fig 1, Supplemental Table 1).…”

“…21 Estimates of the peak plasma levels used the same participant urinary data as above, multiplied by the ratio of peak plasma fluoride levels to urinary excretion (2.6 3 10 3 kg*min/L). 21 To assess the relationship of fluoride excretion to time, the time lapsed with each diaper for participant F was noted and adjusted by measured creatinine per average for the second through the last diaper of that day.…”