Sports Medicine Research: In the Lab & In the Field: Iontophoresis for Drug Delivery. Does it Really Work? (Sports Med Res)
Wednesday, June 29, 2011

Iontophoresis for Drug Delivery. Does it Really Work?

Microdialysis and Delivery of lontophoresis-Driven Lidocaine Into the Human Gastrocnemius Muscle.
Coglianese M, Draper DO, Shurtz J, Mark G. J Athl Train. 2011;46(3):270-6.

Absorption of Iontophoresis-Driven 2% Lidocaine With Epinephrine in the Tissues at 5 mm Below the Surface of the Skin.
Draper DO, Coglianese M, Castel C. J Athl Train. 2011;46(3):277-81.

Like many therapeutic modalities, the clinical efficacy and mechanism of action of iontophoresis remains highly debated. Some clinicians and researchers have doubts about whether iontophoresis can deliver medication to the desired treatment area. To provide further insight into this issue a research group at Brigham Young University published two papers in the Journal of Athletic Training. The first paper (Coglianese et al) used microdialysis, a semi-invasive technique, to collect a small amount of extracellular fluid from localized regions. This technique was thought to be a potential method of determining if iontophoresis-delivered 1% lidocaine (40 mA/min for 10.5 minutes) can penetrate the skin over the triceps surae muscles. The contralateral leg was used as a control site. In all 10 patients (with < 5-mm skin/adipose thickness in the treatment area) they could not detect lidocaine 5 mm deep to the skin surface in the treatment or contralateral legs. However, in a pilot analysis with 3 patients they were able to detect lidocaine at a depth of 3 mm in the treatment leg only. In the second paper (Draper et al) the authors suggested that epinephrine, a vasoconstrictor, might allow lidocaine to penetrate deeper because it may prevent the lidocaine from being picked up by superficial capillaries. In this study, they used 2% lidocaine with epinephrine (40 mA/min for 10.5 minutes and then left the electrodes in place for 50 minutes). Among the 10 participants lidocaine was detected at a depth of 5 mm. The mean volume of recovered lidocaine was 3.63 mg/mL, > 18% of the original drug concentration. This concentration is well above the concentration demonstrated to have therapeutic effects (1 microgram/mL). The authors attribute the success of the second treatment to 1) inclusion of epinephrine, 2) leaving the drug-delivery electrode in place for 50 minutes after the treatment (instead of 30 minutes in the first paper), and 3) selecting a higher concentration of lidocaine (2% instead of 1%).

The greatest lesson from these two studies is the potential influence of the three variables the authors identified (inclusion of epinephrine, duration of passive delivery, and drug concentration). Traditionally, pharmaceutical interventions undergo vigorous testing prior to approval to determine the optimal dose, clinical efficacy, and safety. Iontophoresis and other therapeutic modalities (which may have physiologic effects like pharmaceuticals) do not get tested with the same vigor. Instead of the basic science and clinical trials being completed before the intervention goes public we often end up performing the research after the interventions have been integrated into clinical practice. Clinicians and clinical researchers need to work together to determine what treatment parameters are being used and what are the optimal settings/uses for modalities like iontophoresis. The current studies raise important questions that as a community we need to consider before recommending iontophoresis. For example, what medications, combinations of medications, or medication concentrations are optimal? Are there any additional benefits to leaving the active electrode in place after iontophoresis? As we begin to answer these fundamental questions we will be able to perform well informed clinical trials with patients. What are your opinions about the role of iontophoresis in our treatment protocols?

Written by: Jeffrey Driban
Reviewed by: Stephen Thomas


Greg Barlow said...

I found this article very interesting. Iontophoresis, in theory, seems to make pretty good sense but when it comes to actually applying and testing it on live patients it seems to fall somewhat short. These articles don’t even get into whether or not the treatment is actually effective in doing what it is meant to do. The first article shows right off the bat that the treatment is ineffective at penetrating the skin to a depth necessary for an appropriate treatment. I appreciate the follow up study that was performed although and I apologize for the crude comparison but it feels a little like Mythbusters. They show the first scenario that is in question because most people believe it to be true or it is something commonly done. If they can’t find what they are looking for they move on trying to find what will work. I think in this case what is most commonly practiced is using the 1% Lidocaine and then they manipulated multiple variables to create an effective treatment. They showed great ingenuity in utilizing their knowledge of the body to create an effective protocol. I would imagine that both treatments are equally safe but it would be interesting to see if there were more adverse reactions in the second study compared to the first. Overall, this is what should be done with all treatments and modalities in sports medicine. Before you can begin to evaluate whether the treatment does what you want it to (decrease pain, inflammation, etc.) you need to make sure the theory behind it actually fits what happens in real-life.

Jeffrey B. Driban, PhD, ATC, CSCS said...

Greg: You just hit the nail on the head. "Before you can begin to evaluate whether the treatment does what you want it to (decrease pain, inflammation, etc.) you need to make sure the theory behind it actually fits what happens in real-life."

Medications go through phases of development from creating the molecule, to seeing if it does what it should, to clinical trial phases. While our modalities can have similar physiologic effects we don't make them go through that type of testing. I hope researchers like Draper et al and Dolan et al keep pushing us forward with figuring out some of the fundamental questions and leading us down the path of good clinical trials.

I highly recommend this post as well:
It's another nice study going back to the basics to help us improve the quality of our treatments.

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