Pharmacokinetic differences between sodium fluoride and sodium monofluorophosphate and comparative bone mass increasing activity of both compounds in the rat.

After the administration of an oral dose of 80 mumol/l of NaF (CAS 7681-49-4) to rats, the area under the curve of total plasma fluoride equals 10,200 mumol.min/l. After an oral dose of 80 mumol of monofluorophosphate (MFP/CAS 10,163-15-2), two forms of fluoride appear in plasma: protein-bound MFP and diffusible fluoride. The areas under the curve of total (protein-bound + diffusible) and diffusible fluoride equal 22,200 and 8,850 mumol.min/l, respectively. The activity of MFP for increasing the bone mass of the rat was assessed with NaF as the standard. The animals were treated chronically for 100 days since weaning with food ad libitum and 5 mmol/l NaF, 5 or 2.5 mmol/l MFP solutions as the water supply. The effect obtained with 2.5 mmol/l MFP was similar to that produced by 5 mmol/l NaF, indicating a potency ratio MFP is twice as active as NaF.

Gastric and intestinal absorption of monofluorophosphate and fluoride in the rat.

This paper reports data indicating that, in the rat, sodium monofluorophosphate (MFP, CAS 10163-15-2) is absorbed without hydrolysis through the stomach. This phenomenon and the fact that MFP binds to plasma globulins produce a prompt increase in protein-bound MFP concentration, significantly greater than the increase in plasma ultrafilterable fluoride. Intestinal absorption of MFP was investigated with the isolated duodenal loop in situ. The drug was hydrolyzed to fluoride at the intestinal lumen with a rate of approx. 3 times greater than that for fluoride absorption. After filling the duodenal loop with a MFP solution, ultrafiltrable fluoride accounts for the increase in plasma fluoride concentration, with no evidence of protein-bound MFP. This report also includes analytical techniques for the measurement of MFP in test solutions and in plasma.