Comparison of Thermal Effect with Ultrasound in Rat Calf Muscles after the Application of Five Non-Steroidal Anti-Inflammatory Drugs

Background and Purposes: Phonophoresis has been defined as the migration of drugs through the skin under influence of ultrasound (US). The phonophoresis of nonsteroidal anti-inflammatory drugs (NSAIDs) was studied in vivo through hairless rat skin to determine the temperature changes in superficial and deep tissues in response to NSAID phonophoresis. Study Design and Objectives: To measure and compare the temperature changes in tissues in response to five NSAIDs under phonophoresis. Methods: Male Wistar rats weighing 250 to 350 g had one of five drugs; i.e., piroxicam (Feldene), indomethacin (Indocin), etofenamate (Rheumon), methylsalicylate (Salomethyl), or diclofenac (Voren) applied to one hindlimb followed by phonophoresis. The other hindlimb served as the sham-treated control. US intensities of 1.0W/cm^2 at a fixed frequency of 1 MHz were applied in continuous or pulsed waves with 50% and 25% duty cycles for 5, 10, or 20 minutes. Tissue temperatures were assessed by a digital recorder with hypodermic needle microprobes before and after phonophoresis. Results: Significant temperature rises were produced in skin and muscle after five NSAID phonophoretic and sham treatments. But these temperature rises showed significant differences among five NSAIDs in the deep muscle of phonophoresis-treated limbs (P＜0.05). Especially after piroxicam and diclofenac phonophoresis, the deep temperatures were significantly higher in pulsed-wave US treated limbs than those treated with sham (P＜0.05). Conclusion: The use of piroxicam or diclofenac enhances the thermal effect of deep tissue during US phonophoresis, which may potentially further increase the percutaneous absorption of these drugs.