Fluoride pharmacokinetics during acid-base balance changes in man

Area of Science:

• Pharmacokinetics
• Renal Physiology
• Fluoride Metabolism

Background:

• Fluoride (F) is essential for dental health but its systemic absorption and excretion are influenced by physiological factors.
• Urine pH is a known factor affecting the reabsorption of various substances in the kidneys.

Purpose of the Study:

• To investigate the impact of urine pH on fluoride pharmacokinetics and renal clearance in healthy subjects.
• To determine how induced acidic versus alkaline diuresis affects fluoride elimination from plasma and urine.

Main Methods:

• Administered 3.0 mg fluoride (F) as sodium fluoride tablets to five healthy subjects on two separate occasions.
• Induced acidic urine with ammonium chloride (NH4Cl) and alkaline urine with sodium bicarbonate (NaHCO3).
• Collected serial plasma and urine samples for 12 hours, analyzing fluoride concentrations using a fluoride-sensitive electrode.

Main Results:

• Urine fluoride excretion was significantly lower during acidic diuresis compared to alkaline diuresis.
• Plasma fluoride half-life was longer in acidic urine (4.3 h) than in alkaline urine (2.4 h).
• Renal clearance of fluoride was lower in acidic urine (61.5 ml/min) than in alkaline urine (97.8 ml/min).
• Extra-renal clearance, primarily to bone, was higher during alkaline diuresis.

Conclusions:

• Urine pH significantly influences fluoride elimination and disposition.
• Acidic urine leads to decreased renal fluoride clearance and prolonged plasma half-life, potentially due to increased reabsorption of non-ionic hydrogen fluoride (HF).
• These findings have implications for understanding fluoride dynamics and optimizing fluoride therapy or exposure management.