Population Pharmacokinetics of 38% Silver Diamine Fluoride in Children

Abstract

Purpose: The purpose of this population pharmacokinetic study was to further characterize the pharmacokinetics of silver and fluoride in healthy children 13-months to 13-years of age receiving SDF for the treatment of dental caries.Methods: SDF was applied to lesions teeth of participants, and participants were randomized to blood draw timepoints post-SDF application (early: 2, 4, or 6 hours; intermediate: 24, 48 or 96 hours; and late: 7, 14, or 21 days). Serum fluoride and silver concentrations were determined using fluoride ion selective electrode and inductively coupled plasma-mass spectrometry, respectively. Concentration versus time data were analyzed simultaneously using population pharmacokinetic analysis with nonlinear mixed effects modeling using Phoenix NLMEsoftware. Thirty two children 2-13 years old with at least one carious lesion were recruited at the University of Washington Center for Pediatric Dentistry. The first child began the study on March 21st, 2023 and the last blood sample was taken on June 10th 2023. Results: Twenty-three participants completed the study. Serum fluoride had no discernable temporal pattern. Silver concentrations were best described by a one-compartment model with first-order absorption and elimination following application of SDF. Simulated 12 kg children had a predicted peak concentration that was 3.3-fold higher than simulated 40 kg children (22 ng/mL vs. 6.6 ng/mL) and an exposure that was 2.5-fold higher (60 ng·day/mL vs. 24 ng·day/mL). The simulated half-life was 10.6 days in 12 kg children and was slightly longer in 40 kg children (14.3 days).Conclusions: The observed data and subsequent population pharmacokinetic modeling suggest that the absorption and elimination of silver after SDF application may differ depending on the weight of the child. No fluoride or silver concentrations observed were of clinical or toxicological concern.