Phonophoresis versus topical application of ketoprofen: comparison between tissue and plasma levels.

BACKGROUND AND PURPOSE Over the last few decades, application of ultrasound has been attempted to enhance transdermal transport of several drugs, a method referred to as "phonophoresis." The purposes of this study were to examine the influence of ultrasound on the transdermal delivery of ketoprofen in humans and to compare the concentrations found after continuous and pulsed application. SUBJECTS AND METHODS Twenty-six patients with knee disorders requiring arthroscopy were randomly assigned to 1 of 3 groups. Just before surgery, phonophoresis of a ketoprofen gel (Fastum gel) was given to group A using continuous ultrasound (1 MHz, 1.5 W/cm2, for 5 minutes). Group B received the same treatment but with pulsed ultrasound (100 Hz, 20% duty cycle). Group C received 5 minutes of sham ultrasound with the ketoprofen gel. The ultrasound head was moved over a 10-cm2 area using small, continuous, circular movements. Biopsies of adipose tissue and synovial tissue were taken during surgery to evaluate the local penetration of the drug. Blood samples also were collected to determine whether ketoprofen entered the systemic circulation. RESULTS The concentration of ketoprofen in plasma was negligible in all 3 groups. The concentration of ketoprofen in synovial tissue differed from that in fat tissue. A difference in concentration of ketoprofen in synovial tissue was found between group C and groups A and B. The concentration of ketoprofen in fat tissue and synovial tissue was consistently higher in group B than in group A. DISCUSSION AND CONCLUSION This study confirms that phonophoresis of ketoprofen allows the attainment of higher local concentrations, whereas systemic exposure is lower. The results indicate that, in contrast to sham phonopheresis, ultrasound can increase the transdermal delivery of ketoprofen.