A COMPARATIVE BIOAVAILABILITY STUDY ON 2 NEW SUSTAINED-RELEASE FORMULATIONS OF DISODIUMMONOFLUOROPHOSPHATE VERSUS A NONSUSTAINED-RELEASE FORMULATION IN HEALTHY-VOLUNTEERS

In 12 healthy volunteers the pharmacokinetic parameters of two new sus tained-release formulations of disodiummonofluorophosphate (MFP) (B an d C) were compared with those of a nonsustained-release reference prep aration (A). This randomized study had a single-dose, triple-cross ove r design and consisted of 3 trial days separated by a 1-week washout p eriod. Serial blood samples were obtained over a period of 24 hours an d 24-hour urine was collected. Serum and urine fluoride concentrations were determined using an ion-sensitive electrode (Orion Research). Th e results of this study showed a significant reduction of the area und er the serum concentration versus time curve (AUC) for the sustained-r elease formulations (AUC B: 1487 +/- 354 ng/ ml x hour, AUC C: 1369 +/ - 384 ng/ml x hour) compared with the reference preparation (AUC A: 23 74 +/- 652 ng/ml x hour) (B/A: 63%, C/A: 58%) (P < 0.001). Furthermore , the peak serum concentrations of fluoride (C,,) for B and C (C-maxB: 166 +/- 42 ng/ml, C-maxC: 110 +/- 48 ng/ml) were significantly lower than for A (C-maxA: 380 +/- 77 ng/ml) (P < 0.001). The 24-hour urine f luoride recovery rates were 5.6 +/- 0.7 mg fluoride for A, 3.6 +/- 0.8 mg for B, and 3.2 +/- 1.1 mg for C and corresponded well to the relat ive fluoride bioavailability, as concluded from the serum fluoride con centration. In conclusion, the sustained-release preparations of MFP l ed to a decrease of fluoride bioavailability and avoided high peak ser um concentrations.