Fluoride pharmacokinetics during acid-base balance changes in man

Five healthy subjects were each given fluoride 3.0 mg (F) as sodium fluoride tablets on two occasions - during production of acid urine, induced by giving NH4Cl, and during production of alkaline urine obtained by giving NaHCO3. Frequent plasma and urine samples were taken up to 12 h and were analyzed with a F- sensitive electrode. Control experiments without F administrations were also performed to permit calculation of net F concentration in plasma and urine. The urine F excretion was lower during acid than alkaline diuresis. Pharmacokinetic analysis of the net plasma F concentrations showed that the apparent plasma half-life of F was longer when urine was acid (4.3 +/- 0.6h: SD; n = 5) than when it was alkaline (2.4 +/- 0.4h). This could be explained by changes in the renal clearance of F, which was always lower with an acid (61.5 +/- 8.1 ml/min) than an alkaline (97.8 +/- 10.4 ml/min) urine. The apparent extra-renal clearance, which mainly represents clearance to the bone-pool, was also significantly higher during production of alkaline (109.2 +/- 20.2 ml/min) than of acid (86.3 +/- 21.3 ml/min) urine. It is suggested, that increased reabsorption of non-ionic hydrogen fluoride (HF) is responsible for the decreased renal clearance during acidic conditions.