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Context:In a recent study, we were unable to measure lidocaine in the human calf at a 5-mm depth via iontophoresis. We surmised that this might be due to a lack of epinephrine in the compound. Because epinephrine is a vasoconstrictor, it might allow the drug to pass beyond the capillaries and be delivered to the deeper tissues.Objective: To determine if iontophoresis could deliver lidocaine with epinephrine 5 mm under the surface of human skin, as measured by microdialysis.Design: Descriptive laboratory study. Setting: Therapeutic modalities research laboratory. Patients or Other Participants:Ten volunteers (5 males, 5 females; age, 15-28 years) with less than 5 mm of adipose tissue in the area we measured and with no allergies to lidocaine participated. The measurement area had been free of any injury, swelling, or infection for at least 3 months before the study. Intervention(s):We inserted a microdialysis probe 0.5 cm under the skin of the right lower leg. Next, microdialysis was performed through this area for 60 minutes, which allowed local skin blood flow to return to baseline. We then performed iontophoresis at 40 mNmin using 2 mL of 2% lidocaine. Iontophoresis was performed over this area for 10.5 minutes to collect the lidocaine samples. After this stage, the electrode was left in place for another 50 minutes for a total of 60 minutes. Main Outcome Measure(s):The samples of the drug were analyzed via reverse-phase high-performance liquid chromatography (RP-HPLC) in the chemistry department.Results: The RP-HPLC analysis confirmed the presence of lidocaine in all 10 participants. The mean concentration of lidocaine detected at the 5-mm depth was calculated as 3.63 mg/ mL (greater than 18% of delivered concentration).Conclusions: We found that 2% lidocaine can be delivered up to 5 mm below the surface of the skin when the drug compound contains epinephrine and when passive delivery occurs for at least 50 minutes after the active delivery has terminated.Key Words: drug delivery, diffusion, passive diffusion Key Points• Iontophoresis can be absorbed in tissues to a depth of at least 5 mm.• Microdialysis is an effective tool with which to measure absorption of iontophoretic medication.

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