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Transdermal gabapentin in cats | VETgirl Veterinary Continuing Education Podcasts

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In this VETgirl online veterinary continuing education podcast, we review the use of transdermal gabapentin in cats. I suspect many of you agree that giving gabapentin to fractious kitties prior to veterinary appointments has been an absolute game changer! However, as you can imagine, tasking owners with pilling their emotional feline friends may be asking a lot. Transdermal drugs have made administration of certain medications substantially easier, though these formulations present their own challenges with absorption and bioavailability. Careful testing is required before we can rely upon these therapies enough to recommend and prescribe them. Therefore, in a study by Slovak et al entitled A pilot study of transdermal gabapentin in cats, the authors evaluated gabapentin in a proprietary base called Lipoderm to determine if this transdermal formulation could penetrate feline skin and improve pain scores. The authors explain that this particular base was selected based on previously published literature on its consistency and stability (Zhang; Shakshuki).

To evaluate skin penetration of the medication, the authors performed both in vitro and in vivo testing. Let’s start by discussing the in vitro experiments they performed. In this arm of the study, the authors collected skin from 6 fresh feline cadavers. The gabapentin formulation was applied to two separate regions. One was a shaved area of skin located in the cervical region, 2 cm cranial to the scapula. The other area was a 2.5 cm section of inner ear that was shaved and harvested, which included the epidermis, dermis, and subcutaneous tissue excluding cartilage. Gabapentin (0.1 mL) was applied using a gloved finger to the two locations. It was administered in two concentrations (10% and 20%) after the tissue had been mounted to a diffusion cell. The application occurred at time 0 and again 12 hours later. Samples were then collected from the diffusion cell’s receptor chamber at 0, 2, 4, 12, and 24 hours after the first application of gabapentin. The collected samples were next submitted for gabapentin quantification.

For the in vivo portion of the study, the investigators recruited 8 healthy cats. All were less than 6 years of age. The cats were randomly divided into 4 study groups, based on the dose of gabapentin (5 mg/kg versus 10 mg/kg applied every 8 hours) and the location of gabapentin application (e.g., the ear pinna versus a shaved area of skin in the cervical region). The cats’ owners were provided with gabapentin (250 mg/mL), as well as either disposable finger guards or gloves. The owners were instructed to apply a set volume of the gabapentin to the appropriate location, depending on the cat’s group. The investigators collected blood samples from each cat prior to the first dose, and then at 1 and 5 days after receiving the transdermal gabapentin. Serum was then submitted for gabapentin concentration analysis. One limitation of the in vivo portion of this study is that cats were allowed to groom freely, so it remains possible that cats ingested gabapentin, thereby affecting serum levels. This study also relied on owners to administer medications and adhere to instructions as provided by investigators.

Finally, let’s talk about how the investigators performed the final arm of this study, which was to evaluate pain scores. In this portion of the study, 15 cats diagnosed with either chronic kidney disease (International Renal Interest Society Stage 1 or 2), osteoarthritis, dental disease, or obesity were enrolled. All cats were over 8 years of age and not receiving other medications. The owners of these cats were given gabapentin to apply every 8 hours for 5 days to the inner ear pinna (10 mg/kg per dose). In this portion of the study, the owners alternated between ears for each dose. Then investigators evaluated 2 validated pain assessment scales in each cat. The pain assessment was performed prior to gabapentin administration, then at days 1, 5, and 8 after starting gabapentin. Gabapentin was only given for 5 days total, so for the pain assessment on day 8, the cat had not been receiving medication for 3 days. The authors again collected blood for concentration analysis prior to the first administration of gabapentin, and at days 1 and 5 after starting treatment. Importantly, in this second portion of the in vivo study, the gabapentin administered was compounded by a different pharmacy than the formulation used in the initial in vitro and in vivo phases of the study. The authors later discuss how using compounded gabapentin from two different pharmacies is a limitation of this study.

Okay, let’s talk about some results! First of all, the investigators did detect quantifiable gabapentin at all time points from both ear pinna and cervical skin experiments in the in vitro portion of the study. This also held true in the first arm of the in vivo study. In all 4 experimental groups, gabapentin was detected at both day 1 and day 5. Interestingly, the concentration observed did not differ by dose or skin location. Those results appear quite promising, but of course we also need to know if gabapentin is actually going to improve our feline patients’ pain! That brings us to phase 2 of the in vivo portion of the study. Gabapentin was still detected at days 1 and 5 in these cats, but unlike the initial experiments, the concentration detected was significantly higher at day 5. When the authors evaluated the pre-gabapentin pain scores to pain scores at day 1 and day 5, they found significant improvements on both pain scales between predose to day 5, as well as between day 1 and day 5. Again, these are promising results! Note that the predose pain score did not significantly differ in any cats when compared to day 8, which was 3 days after discontinuing gabapentin administration. In other words, the analgesic effects of this transdermal formulation were no longer observed within three days of stopping therapy.

So what can we take away from this VETgirl podcast? Well, these investigators determined via in vitro and in vivo experiments that administration of transdermal gabapentin will permeate feline skin (both cadaver and live skin) at different anatomic sites, and this treatment was also successful at reducing feline pain scores. Fantastic! The authors discuss various limitations of the in vitro studies, such as small sample numbers and the fact that such experiments cannot perfectly replicate true physiologic conditions. However, by pairing these in vitro experiments with in vivo studies, the investigators were able to provide a bit more clinical insight. Quantifiable gabapentin was detected in the serum of all cats, regardless of site of application, after transdermal administration. The authors do point out that the concentrations detected were quite variable and from a small number of cats, and that reference intervals are not available. However, hopefully such results could be validated in larger studies moving forward. The authors also acknowledge that due to the exploratory nature of the study, no control cats or placebo groups were included for the in vivo portions of the study, and evaluators of pain scores were not blinded. That said, perhaps the most exciting finding in this study was that the authors observed improvements in two separate pain scores following transdermal gabapentin administration (10 mg/kg q8h). Of note, the analgesic effect was no longer present after stopping therapy for 3 days. Despite this study’s limitations, this VETgirl thinks that overall these are promising results. Transdermal administration of gabapentin may be a valuable tool when managing cats with chronic pain, and hopefully we will see more studies like this that advance our knowledge on this important topic.

References:
1. Slovak J, Costa A. A pilot study of transdermal gabapentin in cats. J Vet Intern Med. 2021;35: 1981-1987.
2. Zhang Q, Song Y, Page SW, et al. Evaluation of transdermal drug permeation as modulated by lipoderm and pluronic lecithin organogel. J Pharm Sci. 2018;107:587-594.
3. Shakshuki A, Yeung P, Agu RU. Compounded gabapentin for neuro-pathic pain: stability and beyond-use date (BUD) in some commonly used bases. J Am Pharm Assoc. 2019;59:514-520.

Today’s VETgirl podcast is sponsored by Blue Buffalo, makers of BLUE Natural Veterinary Diets. With a research & development team made up of PhD nutritionists, veterinarians and food scientists with more than 300 cumulative years of experience in the pet food industry, Blue Buffalo is committed to partnering with the veterinary profession and providing the best science-backed care for the pets we love. To learn more about Blue’s commitment and about the Blue Buffalo 6-Point quality process, visit BlueVetConnect.com.

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