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Transdermal drugs and
their use in the treatment
of hyperthyroidism

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by Arnold Plotnick MS, DVM, ACVIM, ABVP

Cats are not easy to medicate.  As a veterinarian specializing in cats, I constantly find myself faced with the dilemma of whether to prescribe an  ideal medication that has to be given three times a day vs. a less-spectacular medication that requires only once-daily medication.  Invariably, I choose the second-rate medication.  Let’s face it: the vast majority of cat owners cannot reliably pill their cat three times a day.  The best medication in the world won’t work if it doesn’t get into the cat.  Asking a cat owner to medicate their cat once a day is reasonable.  Twice a day?  Borderline.  Three times a day?  Nearly impossible.

Our ability to medicate animals is rapidly changing, however, due to the increase in the number of pharmacies now offering the compounding of veterinary medications.  Initially, these pharmacies offered to convert medications that were traditionally available only in capsule or tablet form into a liquid form, as many cat owners find it easier to administer liquid medications to their cat.  These pharmacies soon developed chicken, liver, beef, and tuna-flavored carrier liquids into which the medications were dissolved.  Many cats liked the flavored liquids and would take them voluntarily if offered, although some cats still resisted, not so much due to the taste of the medication, but rather, due to the entire process of medicating.  Cats simply do not like to be told to eat something when they don’t want to.

Pharmacologic therapy by way of the skin offers unique opportunities to deliver medication to a cat.  Transdermal medication (delivered through the skin) is a relatively new science, dating back approximately 20 years or so.  In human medicine, very few medications are prepared this way: nicotine patches to help quit smoking, estrogen patches for hormone replacement therapy, and nitroglycerines for heart disease are a few common examples.  The tremendous growth in the use of compounding pharmacies has given veterinarians the option of providing medications, doses, or formulations that are not readily available from routine sources.  This has now gone beyond reformulating drugs into flavored liquids or into doses that are more appropriate for veterinary patients.  Many of these pharmacies are advocating the use of transdermal gels to deliver medication.  As a veterinarian, I need to know the basics: Do these medications work?  What is the proper dosage to administer?  Are there side effects?

The physiologic function of the skin is to provide a two-way barrier between what’s inside the body, and what’s outside the body.  Transdermal drug absorption involves transgression of this barrier.  Several variables affect the degree of transdermal drug absorption, including the chemical characteristics of the drug, properties of the skin, and the nature of the substance into which the drug has been dissolved (the “vehicle”).  For example, fat-soluble drugs formulated at high concentration will be absorbed to a greater extent than water-soluble drugs formulated at low concentration.    Healthy intact skin generally functions as an effective barrier to drug absorption, whereas diseased skin serves as an ineffective and unpredictable barrier.  The vehicle within which the drug is contained greatly affects the rate and extent of transdermal drug absorption.  Water, alcohol, and dimethyl sulfoxide (DMSO) have all been used, as well as more complex formulations such as ointments, lotions, gels, pastes, aerosols, and creams.

Hyperthyroidism is a common glandular condition in cats.  In many cats, as they get older, the thyroid gland enlarges and produces excessive amounts of thyroid hormones.  The elevated levels of thyroid hormone increase the body’s metabolism, causing a number of clinical signs, the most common being weight loss despite a ravenous appetite. Other clinical signs may include excessive thirst and urination, hyperactivity, diarrhea, panting, excessive shedding, fast heart rate, and a heart murmur.  Surgical removal of the thyroid gland cures the condition, as does destruction of the thyroid gland using radioactive iodine, however, many clients refuse to pursue these avenues due to excessive cost of the procedure, undue risk to the cat, or both.  Most clients choose to administer medication to their cat instead. The medication, methimazole (available in generic form, or as the brand name Tapazole), is administered to cats twice daily.  Medical therapy does not cure the condition. Rather, medication causes the thyroid gland to reduce production of thyroid hormones.  If the medication is not administered in a consistent manner, thyroid hormone levels will begin to rise, and clinical signs will recur.

Because medical therapy of hyperthyroidism is lifelong, and given the difficult nature of administering tablets to cats, several veterinarians have suggested once-daily dosing, citing similar remission rates between once daily dosing and more frequent dosing regiments in human patients with hyperthyroidism.  A recent study presented at the 2001 American College of Veterinary Internal Medicine (ACVIM) Forum, however, in which hyperthyroid cats were given either 5 milligrams of methimazole once a day vs. 2.5 milligrams twice a day, suggested that once daily dosing is considerably less effective than twice daily dosing.  Once again, we’re faced with our basic dilemma of feline pharmacology:  how to get medication into a cat consistently and non-traumatically?

Research involving the use of transdermal methimazole is currently underway, and preliminary results of the studies are promising. A study presented at the 2001 ACVIM Forum, in which 13 cats with hyperthyroidism were administered methimazole gel (applied to the inside of the ear) resulted in clinical improvement in all cats treated.  Most cats gained weight, and clinical signs in many cats improved or resolved.  None of the cats showed clinical side effects.  At the first recheck, approximately 4 weeks after initiating the study, measurement of thyroid hormone levels showed a decrease in 9 of 10 cats, with 7 cats showing normal levels. 

A study presented at the 2002 ACVIM Forum, however, in which methimazole was administered transdermally to healthy cats, gave unexpected results.  In that study, healthy adult cats were given 5 milligrams of methimazole either orally, intravenously, or by way of a transdermal gel.  Blood levels of methimazole were compared for each of the three methods of drug delivery.  The study showed, surprisingly, that methimazole absorption following a single transdermal dose of methimazole gel was variable, but poor in general.  Only two of six cats tested had any detectable methimazole in their bloodstream.  These results seemingly contradict the results reported at the previoius forum, and are in discordance with the increasing number of anecdotal reports apparent efficacy of transdermal methimazole for the treatment of hyperthyroidism.  Reasons for the poor absorption were not cited, however, the researchers emphasized that this study, using healthy cats, involved giving a single dose of transdermal methimazole.  The researchers hypothesized that repeated doses, as required for the treatment of hyperthyroid cats, may enhance absorption of the drug due to changes in the outer layer of the skin that occur when the gel is applied. Additional studies are now underway to better characterize the dosing of transdermal methimazole for the treatment of hyperthyroidism in cats.  Transdermal drug dosing will undoubtedly grow in importance in the coming years, with other classes of drugs, for example, antibiotics, pain medications, and cancer chemotherapy drugs, being formulated for such usage.  Even the most stubborn and disagreeable cat is no match for a quick smear of a measured dose of gel inside the ear.

         

Updated 2/9/06