Pharmacokinetics of Silver Diamine Fluoride in Children

Objectives: 38% silver diamine fluoride is a safe, topical agent used to prevent/arrest caries lesions. Following application, small quantities of silver can be swallowed and absorbed. We conducted a pharmacokinetic study in healthy children, 3-13 years, with ≥1 lesion(s) to determine PK of silver and fluoride.
Methods: Participants were patients at the UCSF Pediatric Dental Clinic. A measured amount of SDF (Advantage Arrest^®) was applied and a blood sample was obtained at one randomly selected timepoint post-application (2, 4, 6, 24, 48, 96,168 hours). Serum F^- was analyzed by ion chromatography and Ag by ICPMS. Parameters were estimated on the pooled naïve sample using Phoenix WinNonlin.
Results: 55 children completed the study and the applied dose ranged from 10-55 mg. Following SDF, serum F^- concentrations ranged from 6-36 ng/mL with no discernable temporal pattern. Ag concentrations ranged from 1.4-46.2 ng/mL. CV at each timepoint ranged from 46% (24-hour) to 148% (48-hour). Given variability, the absorption rate constant was fixed to an estimated value based on adult data (23.7 day^-1, Lin et al.). Predicted C_max was 17.2 ng/mL (SE=1.9) at 5.3 hours (SE=0.52). Area under the serum Ag concentration vs. time curve was 136 ng*hr/day (SE=63). The estimated half-life of Ag was 5.4 days (SE=2.8), which was slightly longer than seen in adults (3.5 days). Predicted C_max was within the range of C_max observed in a study by Vasquez et al. (3-29 ng/mL), though observed Ag concentrations were higher in some children. All Ag concentrations were predicted to drop below the limit of detection (0.1 ng/mL) within ~50 days.
Conclusions: Following SDF treatment, F^- serum concentrations fluctuated around previously reported baseline levels. As expected, some Ag concentrations in children exceeded concentrations in adults, but the variability in Ag and estimated pharmacokinetics of Ag in children were comparable to adults.