Companies Developing More Uses For Iontophoresis

The medical use of electricity dates back at least to the ancient Greeks, who used shocks from electric fish to treat gout. Modern medical researchers are more cautious about applying electrical energy to patients' bodies. Nevertheless, one electrically based technology, called iontophoresis, is growing in popularity, particularly among anesthesiologists and physical therapists. Increasing interest in the technique, which uses electric current to deliver drugs through the skin, has given rise to several companies that offer iontophoresis equipment. Yet some observers express concern that the number of applications may be increasing faster than clinical trials to test their efficacy and safety. Iontophoresis resembles drug patch technology in that it is designed to force substances such as medications and anesthetics through the skin and into the body. It does so by applying a mild electric current to an ionic solution of the substance to be delivered. The technique relies on electrical repulsion: Application of the current drives positively charged molecules in the ionic solution away from an electrode placed above the skin, and hence through the skin and into the tissues. The technique is not applied exclusively to humans. Medical researchers use it to deliver drugs and other chemicals to tissue, frogs' eggs, squid specimens, and the like in laboratory situations, according to Jim Abbott, operations manager at Dagan Corp., a St. Paul, Minn.-based manufacturer of iontophoresis equipment. "We sell mainly to university research laboratories, medical schools and some drug companies," says Abbott. VARIETY OF DEVICES: Dagan Corp's Model 6400 Iontophoresis Generator and Life-Tech's Iontophor-II, a programmable iontophoretic applicator, are two of several products now on the market. However, industry is focused mainly on the use of the technology for relieving human ailments. And indications are that such uses are increasing rapidly. "We offer iontophoresis in physical therapy and pain management," says Katherine Hughey, product manager for iontophoresis at Life-Tech Inc. "Use has more than doubled in the past year." The Houston-based company is the United States' third largest producer of iontophoresis equipment, behind Empi Inc. of Minneapolis and IOMED Inc. of Salt Lake City. Companies are reluctant to provide specific sales figures for their iontophoresis units. According to Hughey, the annual market is roughly $50 million for anesthetic applications and about $20 million for physical therapy. The technique has shown promise in five specific areas: to treat excessive sweating, known technically as hyperhidrosis; as physical therapy to relieve localized pain in muscles and joints; to deliver local anesthetics to the skin and the subcutaneous tissue just beneath it; to carry out sweat testing for cystic fibrosis; and to reduce suffering from shingles, a condition that can cause its victims agonizing pain on their skin. Iontophoresis also is under study in such areas as oncology, lumbar punctures, and pediatric medicine, particularly for children who panic about injections. Dentists have experimented with the technique to treat teeth that are insensitive to cold. Another focus of interest concerns medications that cannot be administered in traditional ways. Some drugs, such as insulin, cannot be given orally because they are hydrolyzed in the digestive tract. Others are excreted or metabolized on their first pass through the body, and hence intravenous administration is not effective. Iontophoresis, its proponents claim, can give more constant concentration of drugs than injection, although not necessarily better clinical efficiency. Iontophoresis devices are relatively simple in design. A battery or rectifier provides the power (batteries are preferable because they are less liable to give patients electric shocks). Most devices also include a current-controlling mechanism to avoid dangerously high currents. Other components of an iontophoresis set-up include current control and meter, voltage control and meter, a timer, and a pulse controller. Beyond the power source, the electrodes are the most critical parts of the device. The return electrode-the one not involved in the actual delivery of medication-is particularly important because it prevents patients from suffering burns during the procedure. The size of units can vary from that of a wristwatch to that of a large book; they can weigh 2 pounds to 4 pounds. To administer iontophoresis, a nurse or technician following a doctor's prescription first cleans the areas of the skin where the electrodes will rest with an alcohol wipe. Then the drug electrode through which the medication is applied is stuck to the skin at the site to be treated. The return electrode is placed a few inches away. The lead wires are connected, and the treatment applied for up to 10 minutes. During that time, a few patients feel a warm, tingly, or prickly feeling, although most report no such effect. Technically, the Food and Drug Administration (FDA) regards therapeutic iontophoresis kits as Class III devices. These require a series of clinical trials of safety and efficacy similar to those imposed on new drugs before they receive so-called premarket approval. However, because such devices were marketed before the government passed the Medical Devices Amendments in 1976, they are cleared for use in approved situations under the much less onerous 501(k) process that applies to grandfathered Class III devices. In other cases, FDA has permitted devices used solely for such specialized applications as diagnosing cystic fibrosis to be regulated as a Class II device. That situation applies to IOMED's Phoresor device, used to deliver the company's Iontocaine preparation of lidocaine for local and skin anesthesia. The fact that FDA regulations require few clinical trials has concerned some observers of the technology. ECRI, a nonprofit health technology assessment group based in Plymouth Meeting, Pa., issued a report on the technology last December, based on an exhaustive study of the medical literature on iontophoresis. "Though iontophoresis has been known for decades," states the report, "there is an absence of clinical trials proving its worth and, most importantly, comparing it to established means of drug delivery such as injection, oral intake, or topical administration." FDA officials did not respond to repeated requests for comment from The Scientist. The report did not go over well with the industry. "We all strongly disagree with it, because there is so much endeavor out there that proves otherwise-clinical studies and other experiments," says Hughey. Priscilla Gunderson, marketing manager for Empi, notes that a few months after the report appeared, some regional office of Medicare decided not to reimburse patients for iontophoresis treatments-although no direct connection can be established between the report and the decision. So far, it seems, the report has not decreased the popularity of iontophoresis treatments. "I'm not aware of any large effect," says Gunderson. "But everyone is concerned about reimbursement issues." Nobody denies that the treatment has its dangers. Burns and shocks are the most common, reported in 10 of 29 studies examined by ECRI. However, manufacturers contacted for the report indicated extremely low rates of such conditions. A few clinical trials indicate a higher rate of burns and shocks; ECRI suggests that the differential figures may result from the fact that clinical trials don't use the latest types of electrode. Why have relatively few clinical trials of the technology taken place? "That's a good question, but there's no clear answer," says Charles Turkelson, an ECRI analyst who prepared the report on iontophoresis. "It's outside the areas of classical clinical research." FOR MORE INFORMATION Technology Assessment Report: Iontophoresis for Drug Delivery (December 1996) is available from: ECRI 5200 Butler Pike Plymouth Meeting, Pa. 19462-1298 (610) 825-6000 - Fax: (610) 834-1275 Dagan Corp www.dagan.com Empi Inc. www.empi.com IOMED Clinical Systems www.iomed.com Life-Tech Inc. www.life-tech.com One possible reason, says Turkelson, is the fact that iontophoresis as now practiced does not require full FDA Class III approval. Another factor makes it difficult to mount any series of integrated studies on iontophoresis: There are no obvious academic centers for research on the topic. "The situation is not at all analogous to, say, transplants," explains Turkelson. "Iontophoresis being fairly new, there are a lot of folk who have published a little." In fact, the analyst continues, that is hardly an uncommon situation with newer medical technologies, particularly of the alternative type. That situation may change as the technology becomes more accepted, and thus attracts the attention of medical research groups. There are indications that teams in university medical centers are beginning to focus on iontophoresis. A group at the University of California, San Francisco, for example, recently developed a method of using the technology to deliver drugs to the sites of localized skin disorders, including nail diseases, herpes lesions, psoriasis, acne, cutaneous T-cell lymphoma, and collagen maladies. SEARCH FOR UNIFORMITY: Oklahoma's Loyd Allen, Jr. developed a computerized power supply and membrane holders for drug diffusion studies. In another research enterprise, a team at the University of Oklahoma Health Sciences Center headed by pharmaceutics professor Loyd V. Allen, Jr. has developed a computerized, low voltage-low current, multiple channel power supply and membrane holders for drug diffusion studies. "We are currently looking at matrix effects on drug flux using in vitro systems," reports Allen. "The ultimate product will be an iontophoresis transdermal patch containing the drug that can be delivered uniformly over a prolonged time period" (L.C. Li, N.J. Vu, L.V. Allen, Jr., "Iontophoresis of cromolyn sodium through mice skin and synthetic membranes," Journal Of Pharmacy And Pharmacology, 44:444-6, 1992). What of scientific opportunities in the area? "They are unlimited, as so many companies are going into it," declares Hughey. "Potentially it's our largest division at Life-Tech." Employment prospects are somewhat confusing for two reasons. Companies hire relatively few scientists to work in iontophoresis; Empi, for example, has a Ph.D. chemist developing the technology and a staff of eight in its clinical research department. And no particular university department or hospital has emerged as a key center for research on the technology. CROSS-DISCIPLINARY TOOL: UT's Arthur Jeske notes that iontophoresis technology can be used in several disciplines. Nevertheless, opportunities do exist for life scientists with an interest in iontophoresis. Guy, for example, worked with 16 postdoctoral and six predoctoral scientists at UC-San Francisco during the past decade. A handful of iontophoresis investigators carries out research and clinical studies at academic institutions in greater Houston, according to Arthur H. Jeske, a professor in the department of basic sciences at the University of Texas Dental Branch in Houston. Another positive point is the fact that iontophoresis can cater to several disciplines. Scientists with experience in clinical departments, anesthesiology, dermatology, physiology, pharmacology, pharmacy, and biophysics are all candidates to join teams studying the technology, says Jeske. "Many times," he adds, "the type of condition you want to deal with using that kind of treatment determines the route you take into the field." (The Scientist, Vol:11, #20, pg 1 and 6, October 13, 1997) Peter Gwynne, a freelance science writer based in Marstons Mills, Mass., can be reached online at PGwynne767@aol.com.

Companies Developing More Uses For Iontophoresis

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