Dexamethasone Sodium Phosphate Penetration During Phonophoresis at 2 Ultrasound Frequencies

Abstract

Context The effect of ultrasound frequency on phonophoresis drug delivery in humans is unknown. Objective To determine if a low (45-kHz) or high (1-MHz) frequency delivered a higher dexamethasone (Dex) concentration through the skin. Design Controlled laboratory study. Setting Laboratory. Patients or Other Participants A total of 40 healthy men between the ages of 18 and 45 years (age = 23.1 ± 2.6 years, height = 176.1 ± 7.2 cm, mass = 88.5 ± 19.4 kg, posterior calf subcutaneous thickness measured using musculoskeletal ultrasound imaging = 0.6 ± 0.2 cm). Intervention(s) Participants were randomly assigned to 1 of 4 groups (ultrasound frequency at microdialysis probe depth): (1) 45-kHz frequency at 1 mm, (2) 45-kHz frequency at 4 mm, (3) 1-MHz frequency at 1 mm, or (4) 1-MHz frequency at 4 mm (n = 10 in each group). Three linear microdialysis probes were inserted at the desired tissue depth. We rubbed dexamethasone sodium phosphate (Dex-P) into the skin and then applied a 15-minute phonophoresis treatment. Main Outcome Measure(s) Dialysate was collected during the treatment and 60 minutes posttreatment and analyzed for Dex-P, Dex, and the metabolite form of Dex. The sum of the 3 analytes was calculated as total dexamethasone (Dex-total), and differences between the 45-kHz and 1-MHz treatment groups were determined by a repeated-measures analysis of variance. Results At 1 mm, 3 (30%) participants in the 45-kHz and 4 (40%) participants in the 1-MHz group had measurable levels of Dex-P. Total dexamethasone increased after the treatment ceased, independent of ultrasound frequency (P < .001), with a trend of the 45-kHz treatment to produce a greater increase in drug concentration (P = .006). At 4 mm, 5 (50%) participants in the 45-kHz and 1 (10%) participant in the 1-MHz group had measurable levels of Dex-P. We observed no difference in Dex-total concentration between treatment groups at 4 mm (P = .72). Conclusions Phonophoresis provided a mechanism for Dex-total delivery at the 1- and 4-mm tissue depths. However, the effectiveness of the ultrasound frequencies varied between the 2 measured tissue depths.