Pharmacokinetics of 38% Silver Diamine Fluoride in Children
- Author(s): Ellenikiotis, Hellene
- Advisor(s): Milgrom, Peter;
- Le, Thuan
- et al.
Objective38% silver diamine fluoride (SDF) is a topical agent used to prevent and arrest caries lesions. Small quantities can be swallowed and absorbed. We conducted a pharmacokinetic study in children, 3-13 y, with ≥1 lesion to determine the pharmacokinetics of silver and fluoride.
MethodsSDF was applied to study participants at the UCSF Pediatric Dental Clinic and blood was obtained at one randomly selected timepoint (2, 4, 6, 24, 48, 96,168 h) post-application. Serum fluoride and silver were analyzed, and pharmacokinetic parameters were estimated using population pharmacokinetic modeling and used to simulate silver exposures in cohorts of children.
Results55 children completed the study (6-10 per timepoint with 10-55 mg SDF applied). Following SDF application, serum fluoride concentrations ranged from 6-36 ng/mL with no discernable temporal pattern. Silver concentrations ranged from 1.4-46.2 ng/mL. A one compartment model with first-order absorption and elimination with weight as a covariate best fit the data. Based on the estimated parameters, silver PK was simulated for cohorts of children from 15 to 50 kg. Compared to previously published data in adults, the predicted time to peak concentration in children was comparable (C: 4.4-5.9 h; A: 5.3 h ± 5.8 h) and predicted peak silver concentrations were within the same range (C: 12.8-22.0 ng/mL; A: 3.0-29.0 ng/mL), though observed silver concentrations were higher in some children. The predicted half-life of silver was longer in children compared to adults (C: 4.0-15.5 d; A: 1.9 ± 1.1 d).
ConclusionsFollowing SDF application, fluoride serum concentrations fluctuated around previously reported baseline levels, and some silver concentrations in children exceeded concentrations in adults. As expected, the predicted silver exposure was greater in children with lower weights. Regardless, low dosage and intermittent use mitigate risk and support continued development of SDF as a minimally invasive, safe, and efficacious treatment for caries in children.