Pharmacokinetic profile of a new fluoride preparation: sustained-release monofluorophosphate

Abstract

The pharmacokinetic profiles of a sustained-release monofluorophosphate (MFP-SR) preparation (76 mg) and of plain MFP (76 mg) were compared in six osteoporotic females. These studies were performed in a randomized, crossover, double-blind design to select a preparation that would result in therapeutic serum levels while avoiding high serum peak values. Following a single dose of 76 mg MFP-SR, the serum fluoride levels remained within the accepted therapeutic range (5-10 microM/liter) for 24 hours. In contrast, following a single dose of 76 mg plain MFP, serum fluoride levels exhibited a wide circadian fluctuation and serum levels approximately threefold higher than those of the MFP-SR preparation (9.5 +/- 1.6 vs 3.5 +/- 0.8 microM/liter, P < 0.005). Compared with plain MFP, the sustained-release MFP had a significantly lower peak concentration (Cmax MFP-SR: 10.6 +/- 3 vs CmaxMFP: 18.9 +/- 5 microM/liter, P < 0.005) and a significantly longer absorption lag time (TmaxMFP-SR 7.3 +/- 1.6 vs TmaxMFP: 3.0 +/- 0.6 h, P < 0.05). Twenty-four-hour urinary fluoride excretion after ingestion of plain or SR fluoride was significantly increased from pretreatment values documenting absorption with either MFP formulation. Our results show that the use of sustained-release MFP preparation that we tested prevents the development of high peak levels associated with the use of plain MFP preparations. Furthermore, a single dose of MFP-SR resulted in serum fluoride levels within the accepted range of 5-10 microM/liter for 24 hours.