Bute and Insulin Issues in Horses

Hello, Summarrians!

This issue discusses some of the ways that drugs are influenced by different metabolisms, which can be critical to how a particular patient responds.

One size does not always fit everyone …

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Laparoscopic Ultrasound in Dogs

This study evaluated the use of laparoscopic ultrasound (LUS) for detecting and localizing liver lesions in dogs with clinical liver disease, comparing its performance to that of preoperative transabdominal ultrasound (TUS). While TUS and CT are common in diagnosing and staging canine liver disease, their accuracy in lesion localization is limited, with reported rates ranging between approximately 52% and 84%. In human medicine, LUS is known to be more sensitive than TUS, CT, and MRI, often identifying additional malignant lesions that can significantly alter surgical plans. In dogs, the research showed that LUS not only detected more liver lesions than TUS—with 71% of cases revealing additional lesions—but also allowed for precise localization of these lesions by directly identifying the corresponding liver lobes. Moreover, in instances where lesions were not visible during the laparoscopic examination, LUS was successfully used to guide biopsies, emphasizing its potential to enhance diagnostic accuracy and inform surgical planning. Although the procedure took longer in dogs with liver lesions compared to healthy dogs, the extended time was attributed to the thorough evaluation required, and the study noted that experience with LUS can reduce the time needed. Despite limitations such as a small sample size and the lack of a gold standard diagnostic comparator like contrast-enhanced CT, the findings support the utility of LUS as a safe and effective adjunctive tool for the diagnosis, staging, and surgical guidance in cases of canine hepatic disease. 

Solari, F. P., Case, J. B., Grosso, F. R. V., Maxwell, E. A., Williams, R. W., Ham, K., & Cabrera, R. (2025). Laparoscopic ultrasonography identifies more liver lesions in dogs compared to transabdominal ultrasonography. American Journal of Veterinary Research https://doi.org/10.2460/ajvr.25.01.0031 

Bottom line — Possible modality option for liver issues.

Phenylbutazone and Insulin Dysregulation in Horses

The study investigated how phenylbutazone, a non-steroidal anti-inflammatory drug, influences insulin dysregulation in horses. Insulin dysregulation involves both hyperinsulinemia and tissue insulin resistance, which can occur separately or as compensatory responses to one another. Unlike observations in rodent models and human type-2 diabetes—where NSAIDs tend to increase insulin secretion and reduce insulin clearance—phenylbutazone in horses reduced blood glucose and serum insulin concentrations during an oral glucose test, an effect not mediated by the enteroinsular axis. Using methods such as the mFSIGTT and minimal model analysis, the research revealed that the improvement was largely due to enhanced tissue insulin sensitivity, evidenced by an increase in insulin sensitivity (SI) without significant changes in pancreatic insulin secretion (AIRg) or overall β-cell responsiveness (DI). Although the anti-inflammatory properties of phenylbutazone, potentially augmented by sodium salicylate in its formulation, may explain the improved tissue response, the modest improvements and inherent side effects of long-term NSAID use limit its clinical relevance for managing equine insulin dysregulation and laminitis-associated pain. 

Kemp, K.L., Yuen, N.K.Y., Skinner, J.E. and Bertin, F.-R. (2025), Effect of Phenylbutazone Administration on Insulin Sensitivity in Horses With Insulin Dysregulation. J Vet Intern Med, 39: e70028. https://doi.org/10.1111/jvim.70028

Bottom line — Modest effect could help in the short term

Differences in Drug Metabolism in Dogs

This study examined the variability in drug metabolism mediated by canine CYP2D15, an enzyme analogous to human CYP2D6, which is responsible for metabolizing a wide range of medications. Researchers used an in vivo approach with the PrIMe cocktail, administering dextromethorphan as a probe to assess CYP2D15 activity, and then measured the metabolite-to-parent drug ratio in urine to gauge enzyme performance. The findings revealed significant interindividual variability in metabolism among dogs, with breed emerging as a key factor. For instance, Golden Retrievers generally exhibited faster metabolism, whereas pugs tended to metabolize drugs more slowly. Mixed-breed dogs showed a broad range of metabolic values, likely reflecting their genetic admixture. 

In addition to breed differences, the study evaluated the association of specific CYP2D15 genetic variants with enzyme activity. Although a weak link was observed between the p.Gly186Ser variant and reduced metabolic rate, this effect was modest, implying that other genetic factors might contribute to the observed variability. No clear associations were found with age or sex, and while body weight showed a slight effect in univariate analysis, it lost significance when breed was taken into account. Overall, the research underscores that, like human CYP2D6, canine CYP2D15 displays high variability in drug metabolism, though the precise genetic underpinnings remain to be fully clarified, warranting further investigation. 

Jimenez, T. P., Trostle, M., Zhu, Z., Martinez, S., & Court, M. H. (2025). Dextromethorphan phenotyping of healthy pet dogs reveals breed-associated differences in cytochrome P450 2D15–mediated drug metabolism. American Journal of Veterinary Research https://doi.org/10.2460/ajvr.24.12.0377 

Bottom line — Could help some day in more accurate dosing regimes.

Just putting things in perspective …