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Fluoride pharmacokinetics in infancy
J Ekstrand1, S J Fomon, E E Ziegler
1Department of Dental Toxicology, Karolinska Institute, Huddinge, Sweden.
Insights
Infant fluoride supplementation shows significant absorption and retention, with excretion rates varying by urinary flow and age. Fluoride clearance decreases with age, indicating altered pharmacokinetics in infants.
Area of Science:
- Pharmacokinetics
- Pediatric Medicine
- Toxicology
Background:
- Infants require careful consideration for fluoride supplementation due to developing physiology.
- Understanding fluoride absorption, distribution, metabolism, and excretion (ADME) is crucial for safe dosing.
- Limited pharmacokinetic data exists for fluoride supplementation in the infant population.
Purpose of the Study:
- To characterize the pharmacokinetic profile of a fluoride supplement in infants.
- To assess fluoride absorption, retention, and excretion following supplementation.
- To investigate the relationship between fluoride dose, body weight, age, and pharmacokinetic parameters.
Main Methods:
- A crossover study design involving 17 infants receiving either a fluoride supplement or placebo.
- Plasma and urine samples collected over 5 hours post-administration for fluoride analysis.
- Pharmacokinetic parameters including peak plasma concentration, area under the curve, and clearance were calculated.
Main Results:
- Fluoride supplementation led to a mean peak plasma concentration of 3.3 µmol/L, reached within 30-60 minutes.
- Fluoride retention ranged from 75.4% to 87.6% of the absorbed dose, strongly related to body weight.
- Urinary excretion correlated with urinary flow, and plasma clearance decreased significantly with increasing age.
Conclusions:
- Infants demonstrate significant absorption and retention of supplemented fluoride.
- Age-dependent changes in plasma clearance suggest altered renal handling of fluoride in infants.
- These findings are critical for establishing safe and effective fluoride dosing guidelines for infants.
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 mumol/kg (2.9 micrograms/kg), and plasma fluoride concentrations ranged from 0.05 to 0.11 mumol/L (10 to 20 micrograms/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 mumol/kg (36.6 micrograms/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 mumol/L (63 ng/mL). Area under the plasma concentration curve averaged 236 nmol.m-1 x min (4479 ng.mL-1 x 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-1 x min-1 and decreased significantly with age. Net fractional clearance (renal clearance of the fluoride dose/GFR) averaged 56.7%, which was significantly greater than the 29% observed during the control studies.(ABSTRACT TRUNCATED AT 250 WORDS)