Is there any information regarding uptake, risk for accumulation or adverse effects after oral admi

Fråga: Is there any information regarding uptake, risk for accumulation or adverse effects after oral administration of ordinary doses of sodium fluoride (Dentan) (6 x 0.25 mg) daily in dialysis patients?

Sammanfattning: Sodium fluoride treatment in patients with renal failure should be avoided because of a risk of accumulation and fluorosis. It is uncertain whether intermittent dialysis is sufficient to prevent accumulation. Topical treatment is therefore preferred.

Svar: This question has been answered before in Drugline. According to this document sodium fluoride is extensively excreted via glomerular filtration. Accumulation occurs in patients with renal failure followed by an increased risk of fluorosis and bone fragility. Accumulation occurs even if the dose is lowered due to impaired renal excretion. Fluoride treatment to patients with renal failure is best avoided (1).

Sodium fluoride is rapidly absorbed from the gastrointestinal tract and measurable concentrations could be found in plasma within one hour. Fifty per cent of the dose of sodium fluoride is deposited predominantly in the skeleton and teeth and 50 per cent is excreted in the urine in normal objects without renal failure (2).

Increasing age is associated with decreasing renal function and a secondary increase in sodium fluoride (3). Anuric patients cannot excrete the ion and the clearance is therefore dialysis dependent, or to a small extent, regulated by a compensatory excretion in the feces. During hemodialysis sodium fluoride disappears from plasma through diffusion, as the dialysis solution does not include this specific electrolyte. Thus elimination only occurs intermittently as a normal hemodialysis schedule is 4-5 hours three times a week. The clearance might not be sufficient and thus accumulation occurs.

Concomitant administration of calcium carbonate (which is in general administered to patients with severe renal failure) reduces the bioavailability by 30 to 40 per cent (4). The effect on accumulation in patients with renal failure is not known. 1 Drugline no 08033 (year 1990) 2 Sodium Fluoride. Drugdex(R) System; Micromedex, Inc., Englewood, Colorado (Edition expires (date 9/2000) 3 Murray TM, Harrison JE, Bayley TA, Josse RG, Sturtridge WC, Chow R, Budden F, Laurier L, Pritzker KPH, Kandel R, Vieth R, Strauss A, Goodwin S: Fluoride treatment of postmenopausal osteoporosis: age, renal function, and other clinical factors in the osteogenic response. J Bone Mineral Res 1990; 5(suppl 1): S27-S35 4 Ekstrand J, Spak CJ: Fluoride pharmacokinetics: its implications in the fluoride treatment of osteoporosis. J Bone Mineral Res 1990; 5(suppl 1): S53-S61 (Medline abstract)