Tolerance of low-frequency ultrasound sonophoresis: a double-blind randomized study on humans.

Background: Sonophoresis [low-frequency ultrasound (US)] has been used in animals and in vitro to investigate enhanced percutaneous absorption of drugs. No study focused on its clinical human tolerance has been published as yet.

Methods: We aimed to assess the bioeffects of low-frequency US in vivo on human skin in a double-blind randomized-controlled study. We applied pulse-mode US at 36 kHz for 5 min in a step procedure of increasing dosage, from 1.57 to 3.50 W/cm(2), and placebo. The primary outcome was toxic effects of the procedure, defined as a pain score >40 on a 0-100 mm visual analogue scale or necrosis. Erythema (scored from 0 to 3 in severity) was also evaluated. The secondary outcomes were measurements of skin thickness by high-resolution skin imaging, of skin capacitance and temperature.

Results: We included 34 healthy volunteers. We found no pain score >38 and no skin necrosis with either US or placebo. Erythema was systematically observed immediately after US application, but after 1 day, we observed three cases in the knee group. The most frequent adverse effect was tinnitus. We observed no marked increase in temperature or cutaneous thickness after US or placebo. Cutaneous capacitance increased immediately after both applications.

Conclusion: Such data demonstrating good tolerance of sonophoresis can be useful before the initiation of a clinical trial of the therapeutic use of low-frequency sonophoresis in humans.