Pharmacokinetics of ingested fluoride: lack of effect of chemical compound.

UNLABELLED: Fluoride in drinking water may be present from natural sources or added as sodium fluoride (NaF), sodium silicofluoride (Na(2)SiF(6)) or fluorosilicic acid (H(2)SiF(6)). Results from an early study with rats suggested that, when ingested as Na(2)SiF(6), the absorption and excretion of fluoride were greater than when ingested as NaF. OBJECTIVE: The present single-blind, crossover study with 10 adults was done to determine three key pharmacokinetic parameters: the maximum plasma fluoride concentrations (C(max)), the elapsed time to reach the maximum concentrations (T(max)) and the 6-h areas under the time-plasma concentration curves (AUCs) after ingestion of 500 mL of water containing 0.67 or 5.45 mg F/L present naturally or added as NaF or H(2)SiF(6). DESIGN: Blood was collected prior to and at nine time points during 6h after ingestion of the test solutions. Plasma was analysed by electrode after HMDS-facilitated diffusion and the data were analysed for statistically significant differences using repeated measures ANOVA. RESULTS: The C(max), T(max) and AUC values after ingestion of the solutions containing natural fluoride, NaF or H(2)SiF(6) did not differ significantly at either dose level. Further, the T(max) values associated with the 0.67 and 5.45 mg/L solutions did not differ significantly indicating that the absorption, distribution and elimination rates were not affected by the dose size. CONCLUSIONS: Considered together with published reports, the present findings support the conclusion that the major features of fluoride metabolism are not affected differently by the chemical compounds commonly used to fluoridate water nor are they affected by whether the fluoride is present naturally or added artificially.

Silicic acid: its gastrointestinal uptake and urinary excretion in man and effects on aluminium excretion.

Silicon (Si), as silicic acid, is suggested to be the natural antidote to aluminium (Al) toxicity, and was recently shown to promote the urinary excretion of Al from body stores. The metabolism of Si in man, however, remains poorly investigated. Here we report on the pharmacokinetics and metabolism of Si in healthy volunteers following ingestion of orthosilicic acid (27-55 mg/l Si) in water. We also investigated whether orthosilicic acid promotes the urinary excretion of endogenous Al. Minimum, median uptake of Si from the ingested dose was 50.3% (range: 21.9-74.7%, n = 8) based on urinary analysis following dosing. Significant correlations were observed between creatinine clearance and Si levels in serum or urine (r = 0.95 and 0.99, respectively). Renal clearance of Si was 82-96 ml/min suggesting high renal filterability. These results suggest that orthosilicic acid is readily absorbed from the gastrointestinal tract of man and then readily excreted in urine. There was no significant increase in Al excretion, over 32 h, following ingestion of the orthosilicic acid dose (P = 0.5; n = 5).

Precipitation and characterization of an aluminosilicate from AlCl3-Na2SiO3-HCl in serum, of interest for Alzheimer disease.

A precipitation experiment was performed with human serum to model aluminosilicate formation in brains of patients with Alzheimer disease. Aluminum and (or) silicate ions were added to serum in a 1:2 molar ratio at pH 7.4. Precipitates formed immediately and were left for 24 h at 37 degrees C before filtration. Silicate and aluminosilicate formed precipitates with human serum proteins albumin, transferrin, and IgG. In untreated samples, the IgG/albumin ratio increased slightly compared with the ratio in dried serum. Diethylbarbiturate-washed precipitates had a significantly lower protein content than did untreated ones. The IgG/albumin ratio increased considerably in the sample containing aluminosilicate. We conclude that IgG is the sodium dodecyl sulfate-soluble human protein most firmly bound to the aluminosilicate matrix. From 27Al magic-angle-spinning nuclear magnetic resonance (MAS NMR), a pronounced peak was found at 52.79 ppm and a minor peak at 0.53 ppm, suggesting that 4-coordinated aluminum predominates and that 6-coordinated aluminum is present in a smaller proportion. The 29Si MAS NMR spectrum shows a poorly ordered structure. The aluminosilicate formed also contains the cations Na+ > K+ > Ca2+ > Mg2+ and anions Cl- > PO4(3-). Rather than looking for aluminum toxicity to explain the effects of Alzheimer disease, one should consider that by precipitating such a composite phase, the balance of cations, anions, and proteins in human serum is changing.

The effects of antacids on the absorption of enteric-coated phenylbutazone (butacote).

Phenylbutazone bioavailability from an enteric-coated formulation (Butacote) has been studied in normal volunteers following ingestion of a single 200 mg dose with water, aluminium hydroxide and magnesium trisilicate. No significant alteration in bioavailability of phenylbutazone from Butacote was noted in the presence of the antacids.

Effect of sialidase on the viability of erythrocytes in circulation.

Sialic acid has been detected on the erythrocyte surface of a number of different species of animals. The objective of this investigation was to determine the physiological significance of these sialyl residues to the viability of erythrocytes in circulation. Methods have been described for the determination of total sialic acid on red blood cells and the conditions under which it may be released with sialidase. Chicken, dog, goat, and rabbit were chosen for these studies because of the differences in the amount (3 X 10(6) - 72 X 10(6) resides per erythrocyte), and type (N-acetyl-or N-glycolyl-neuraminic acids) of sialic acid found on the surface of their erythrocytes. Radioactive tagging with Na251CrO4 was used to monitor the effect of sialidase on the viability of erythrocytes upon autologous transfusion. By the two criteria used to assess the viability of erythrocytes-the percentage of erythrocytes surviving 24 hr after the autologous transfusion, and the half-life of those red blood cells in circulation that survive the first 24 h after the autologous transfusion, and the half-life of those red blood cells in circulation that survive the first 24 hr-it is apparent that the presence of sialic acid on the cell surface is crucial for the survival of nonnucleated mammalian erythrocytes. The loss of viability of dog erythrocytes can be elicited by the removal of approximately 10% of the total sialic acid. In marked contrast to the behavior of mammalian erythrocytes, sialidase-treated chicken erythrocytes appear to retain their viability in circulation.