Fluoride bioavailability after intravenous and oral administration: Importance of renal clearance and urine flow

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Abstract
Fluoride (3 mg) was administered as a continous intravenous infusion during 30 min to 6 healthy subjects. Plasma concentrations and urinary excretion of fluoride in these experiments were compared with those obtained following oral administration of 2.82 mg, 4.50 mg, 5.64 mg, and 9.40 mg in the form of tablets and capsules. There were large day-to-day variations in the renal clearance of fluoride. This was shown to be due to differences in the urinary flow, an increase in flow causing an increase in renal clearance. The mean value of renal clearance from all experiments was 66.2 ± 27.8 (SD; n = 16) mllmin. The extrarenal clearance, suggested to represent mainly the clearance to the bone pool, showed less interindividual variation: mean 110.3 ± 32.3 (SD; n = 6) ml/min; the fraction remaining in the bone pool was highly consistent: 0.579 ± 0.049 (SD; n = 6). When apparent bioavailability was calculated from plasma and from urinary data, there was a great intra- and intersubject variation, as well as poor agreement between the two methods of calculations. This was found to be due to the day-to-day variation in renal clearance, which, in turn, varied with urinary flow. By use of equations that corrected for these variations, it was found that the bioavailability of sodium fluoride tablets is approximately 100%.

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