Kinetic model of fluoride metabolism in the rabbit

Sodium fluoride, in small doses, was given to rabbits intravenously or by stomach tube, and the appearance of fluoride in the blood and urine was then monitored frequently over the next 10 hours. Compartmental analysis of the data yielded a kinetic model of fluoride metabolism comprising gut, extracellular fluid (including plasma), urine, short term nonexchangeable bone, exchangeable bone, and intracellular fluid. Fractional transfer rates and the content curve were obtained for each compartment. The results indicated that under steady state conditions approximately 15% of fluoride ingested in food and water was absorbed by the rabbit. The absorbed fluoride entered the extracellular fluid pool, where portions exchanged with fluoride in the tissues and bone. An equivalent amount, i.e., 15% of the intake, was then excreted in the urine. It is interesting to note that in this species a store of fluoride was required in the gut to sustain the steady state. Fecal excretion of fluoride was equivalent to 85% of that ingested. Rate constants calculated for the various transfers indicated that removal of fluoride from the extracellular pool into the nonexchangeable bone compartment was approximately three times more rapid than was removal by excretion into urine. Results of a study with a tracer dose of fluoride, 3 pg of F, gave results in good agreement with those predicted by the model, which was derived from experiments utilizing doses of about 1.5 mg. This suggested that the response is linear over a large dose range.