Treating cats with chronic kidney disease generally requires daily administration of an antiproteinuric drug, which can impact medication compliance with medical outcomes as well as negative implications for the wellbeing of the cat and the owner. In addition, for a given daily dose, benazepril is more effective when administered several times a day but this could increase non compliance. It was therefore conceived to incorporate benazepril into a highly palatable diet for cats with chronic kidney disease, that is, a medicated diet, that the cats could consume throughout the day, with the aim of replacing multiple administrations thanks to the cat's nibbler eating behavior and the slow gastric emptying in cats eating dry food. Our investigation showed that Consumption of the medicated diet led to an overall lower drug exposure in both healthy and CKD cats compared to benazepril once-daily tablets. Nevertheless, the overall efficacy in inhibiting ACE was at least equivalent (CKD cats) and even higher (healthy cats). In both cases, this resulted in greater efficiency (i.e., the amount of desired therapeutic effect produced per unit of drug exposure) of the medicated diet than of conventional once daily tablet administration. More broadly, this observation suggests that the temporal pattern of benazepril exposure may be more important than the total dose administered. Medicated diets may represent a new strategy for improving both compliance and therapeutic efficiency in chronic feline diseases, provided that the diet is well accepted by the cat.

We investigated seasonal variation in the office and ambulatory blood pressure control in hypertensive patients treated with two single-pill dual-combination antihypertensive therapies. The study participants (n = 560) were hypertensive patients enrolled in a 24-week therapeutic study. Antihypertensive treatment was initiated with amlodipine/benazepril 5/10 mg/day or benazepril/hydrochlorothiazide 10/12.5 mg/day, with the possible up-titration to 10/20 mg/day or 20/25 mg/day during follow-up, respectively. Office blood pressure was measured at each clinic visit, and ambulatory blood pressure monitoring was performed at baseline and 24-week follow-up. At 24 weeks of follow-up, in patients who continued antihypertensive treatment (n = 511), the proportion of up-titration to higher dosages was significantly different across seasons of treatment commencement in the benazepril/hydrochlorothiazide group (P = 0.002), but not in the amlodipine/benazepril group (P = 0.84). The between-group difference was significantly different in 134 patients who commenced treatment in winter (18.9% vs. 5.0%, P = 0.02), but not in 377 patients who commenced treatment in the other seasons (P ≥ 0.33). The control rate of office blood pressure (<140/90 mmHg) was significantly different across seasons of treatment commencement in the amlodipine/benazepril group (P = 0.01), but not in the benazepril/hydrochlorothiazide group (P = 0.16). The mean changes from baseline to 24-week follow-up tended to be smaller in the benazepril/hydrochlorothiazide than amlodipine/benazepril group in 24-h (mean between-group difference, -2.8 mmHg) and daytime diastolic blood pressure (mean between-group difference, -3.2 mmHg) in patients who commenced treatment in winter, though statistical significance was not achieved (P ≥ 0.07). In conclusion, there was seasonality in the clinic and ambulatory blood pressure-lowering effect of antihypertensive drug combinations, with a marginally significant difference in treatment intensity and blood pressure control between treatment with amlodipine or hydrochlorothiazide in combination with benazepril.

This study evaluated the chemical and microbiological stability of six oral liquid formulations, benazepril hydrochloride, candesartan cilexetil, disulfiram, fluconazole, methocarbamol, and pentoxifylline, compounded in the suspending vehicle SyrSpend® SF PH4. Stability-indicating UHPLC methods were validated for each API and confirmed to be specific, precise, accurate, and linear within the analytical ranges tested. Forced degradation studies ensured method suitability for detecting potential decomposition pathways. Chemical stability was assessed over 90 days under room temperature and refrigerated storage, alongside pH monitoring and visual inspection. Antimicrobial effectiveness testing (USP <51>, Category 3: oral aqueous products) demonstrated that all formulations met preservative efficacy criteria at the final assigned BUD. Results revealed API-specific stability profiles: several formulations remained within 90-110% of label claim for up to 90 days, while others showed temperature degradation patterns dictating shorter BUDs. Overall, SyrSpend® SF PH4 proved to be a versatile and reliable vehicle for compounded oral liquids, supporting extended BUDs while maintaining physicochemical integrity and microbiological quality. These findings reveal dependent degradation patterns that dictate shorter BUDs. Overall, SyrSpend® SF PH4 proved to be a versatile and reliable vehicle for compounded oral liquids, supporting extended BUDs while preserving physicochemical integrity and microbiological quality. These findings provide evidence-based guidance for compounding pharmacists and reinforce the role of SyrSpend® SF PH4 in personalized pharmacotherapy.

Because of the low levels of benazepril in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants.

In 2025, 3 novel pharmaceutical agents for small animals were released on the German veterinary medicinal products market: the 2 Janus kinase inhibitors atinvicitinib and ilunocitinib for the treatment of pruritus associated with allergic or atopic dermatitis, and the serotonin reuptake inhibitor fluoxetine for the adjunctive treatment of separation-related behavioral disorders. No active substance received an extension to additional animal species. New to the market for small animals are: 2 active substances (benazepril, pimobendan), each with a new dosage form; one active substance (meloxicam) with a new dosage form and content of active substance; 3 active substances (enflicoxib, milbemycin oxime+praziquantel, tramadol) with new content of active substance, a new combination of active substances (terbinafine+betamethasone acetate), and 2 active substances (metoclopramide, mirtazapine) with new package sizes. There were no new vaccines for small animals in 2025.

Hypertension is a well-established risk factor for myocardial ischemia, which may often remain asymptomatic. This study aims to evaluate the effects of diltiazem on blood pressure and myocardial ischemia in patients with grade I-II primary hypertension. Between January 2018 and April 2022, 160 patients diagnosed with mild to moderate primary hypertension were enrolled. Patients were assigned to 1 of 4 treatment groups: benazepril monotherapy group (benazepril 10 mg/day, n = 44); irbesartan monotherapy group (irbesartan 150 mg/day, n = 45); diltiazem monotherapy group (diltiazem hydrochloride sustained-release tablets 90 mg/day, n = 36); and combination therapy group (diltiazem hydrochloride sustained-release tablets 90 mg/day plus either benazepril 10 mg/day or irbesartan 150 mg/day, n = 35). Systolic and diastolic blood pressure were recorded at baseline and post-treatment. Myocardial ischemia was assessed using 24-hour Holter electrocardiogram monitoring, and the total ischemia burden (TIB) was calculated as the cumulative duration of ST-segment depression. All treatment groups demonstrated statistically significant reductions in both systolic and diastolic blood pressure following intervention (P < .05). The combination therapy group exhibited a significantly greater reduction in diastolic blood pressure compared to the diltiazem monotherapy group (P < .05). TIB significantly decreased in the diltiazem monotherapy, benazepril monotherapy, and combination therapy groups (P < .05), whereas the reduction observed in the irbesartan monotherapy group was not statistically significant. Additionally, the benazepril monotherapy group demonstrated a significantly greater reduction in TIB compared to irbesartan (P < .05). Diltiazem effectively reduced both systolic and diastolic blood pressure and demonstrated anti-ischemic properties. Combination therapy with diltiazem and other antihypertensive agents, particularly benazepril, may offer additional therapeutic benefits. These findings support the potential role of diltiazem in the management of patients with mild to moderate hypertension and subclinical myocardial ischemia.

Cardiorenal syndrome in dogs, particularly those with myxomatous mitral valve degeneration (MMVD), involves complex neurohormonal interactions, yet molecular mechanisms linking heart and kidney dysfunction remain poorly understood. This study aimed to identify serum peptide and protein signatures that differentiate disease stages and clarify pathophysiology. We hypothesized that alterations in the serum peptide mass fingerprint and protein profile would serve as sensitive biomarkers for kidney disease progression in MMVD-affected dogs. Dogs were classified into five groups following ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dog and IRIS Staging of chronic kidney disease (CKD): Healthy, MMVD Stage B1, MMVD Stage C without azotemia, MMVD Stage C with azotemia, and CKD IRIS Stage 2. Serum peptide profiling was performed using Matrix-Assisted Laser Desorption/Ionization - Time-of-Flight Mass Spectrometry (MALDI-TOF MS) for peptide mass fingerprint analysis and Nanoscale Liquid Chromatography-Tandem Mass Spectrometry for protein identification. MALDI-TOF MS effectively discriminated healthy dogs from diseased groups through discrete clustering in Partial Least-Squares Discriminant Analysis plots. Proteomic profiling identified 100 statistically significant proteins, with a critical subset of shared proteins including Peroxisomal biogenesis factor 14, Glutaredoxin-2, Creatine kinase mitochondrial 2, and Selenocysteine insertion sequence-binding protein identified between the MMVD C WAZ and CKD Stage 2 groups. These proteins are associated with the arginine and proline metabolism and peroxisome pathways, which were found to be influenced by standard medications such as pimobendan, furosemide, spironolactone, benazepril, and sildenafil. These findings reflect a systemic failure of cellular redox and energetic homeostasis driven by renin angiotensin aldosterone system activation and oxidative stress. The convergence of peroxisomal and mitochondrial dysfunction suggests a unifying mechanism for parallel cardiac and renal deterioration. These proteomic markers persist despite standard medical therapy, highlighting their potential as auxiliary tools for risk stratification and the monitoring of treatment efficacy in canine cardiorenal syndrome.

Results from the ACCOMPLISH (Avoiding Cardiovascular Events through COMbination Therapy in Patients LIving with Systolic Hypertension) trial suggest that combining benazepril with amlodipine, rather than hydrochlorothiazide, provides superior cardiovascular protection potentially in a BP-independent manner. We employed random survival forest, a powerful machine learning approach, to compare the relative importance of risk factors (i.e., variable importance factor (VIF)), focusing on in-trial BP control for predicting the primary composite cardiovascular outcome in the 2 treatment limbs. Among the 6 risk factors with significantly different VIFs between treatments, all were lower under benazepril/amlodipine combination. The VIF for achieved systolic BP at 6-months was 35% lower in the benazepril/amlodipine (0.082) versus the benazepril/hydrochlorothiazide (0.126) limb. The fact that in-trial BP control was less important for preventing cardiovascular events during benazepril/amlodipine treatment provides novel support for our contention that this combination regimen provides a degree of clinically-relevant cardio-protective actions in a BP-independent manner.

Benazepril, an angiotensin-converting enzyme (ACE) inhibitor, is widely prescribed for the management of hypertension and heart failure. The cost and efficiency of its production are strongly influenced by the synthesis of a key intermediate, 3-bromo-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one. Conventional synthetic routes often involve multiple steps, high raw material consumption and extensive solvent use, which limit scalability and compromise environmental sustainability. To develop a streamlined, cost-effective and greener synthesis of Bromo-benzo[b]azepinone Intermediate for Benazepril that improves scalability, reduces costs and delivers high product quality with minimal environmental impact. The optimized process combines electrophilic bromination of α-tetralone with subsequent oxime formation in a telescoped sequence, reducing solvent usage and operational steps. The oxime undergoes C-N aryl migration via a Beckmann rearrangement using Eaton's reagent-a greener, more efficient alternative to polyphosphoric acid-enhancing reaction control and product quality. Reaction conditions, purification strategy and solvent recovery were systematically refined to maximize efficiency and sustainability. The developed process yielded the target intermediate in 78% yield with > 95% purity, while improving operational efficiency and minimizing waste. Telescoping the bromination and oxime formation steps reduced by-product formation and simplified work-up, resulting in a cleaner product. Replacing polyphosphoric acid with Eaton's reagent improved reaction efficiency, eased handling and lowered environmental impact. Together, these innovations reduced raw material costs substantially and delivered a robust, scalable process. The developed process demonstrates the benefits of step telescoping and the use of Eaton's reagent for Beckmann rearrangement, providing improved reaction control, easier handling and enhanced selectivity compared with conventional polyphosphoric acid systems. The strategy reduces operational steps and purification requirements, improving process efficiency and lowering waste generation. These improvements enhance the overall sustainability and economic feasibility of the process, making it suitable for scalable industrial production. This optimized synthetic route for 3-bromo-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one is efficient, scalable, and environmentally sustainable. By integrating step telescoping with greener reagents, the process meets industrial pharmaceutical manufacturing goals, offering both economic advantages and environmental benefits in Benazepril production.

This paper presents a sustainable chromatographic framework using reverse-phase liquid chromatography (RPLC) method with an ultraviolet detector (UV) to determine the ionization behavior of three angiotensin-converting enzyme (ACE) inhibitors, benazepril, cilazapril, and quinapril, in a water-organic solvent binary mixture. In this study, retention-mobile phase pH data under various hydroorganic conditions were analyzed using nonlinear regression (NLREG) and linear solvation energy relationship (LSER) approaches to calculate the dissociation constant (pKass) values of the compounds. Accurate aqueous pKa (pKaww) values are essential for predicting ionization-dependent solubility, chromatographic behavior, and biopharmaceutical performance of ACE inhibitors. Chromatographic experiments were conducted at 25 °C and 37 °C on a YMC Triart C18 column in ethanol-water, methanol-water, and acetonitrile-water mixtures (40-55% v/v). The pKaww values of the compounds in aqueous medium were calculated using two different temperatures and approaches. At 37 °C, pKa1ww values for cilazapril, benazepril, and quinapril were calculated as 3.715, 3.819, and 3.967, respectively; and pKa2ww values were calculated as 5.316, 5.187, and 5.226, respectively. The values calculated from these studies are compatible with each other and with the literature values. The dependence of the developed methods on twelve green analytical chemistry (GAC) principles was evaluated using the Analytical Greenness Metric (AGREE score=0.77), the Green Analytical Procedure Index (GAPI), and the Analytical Green Star Area (AGSA score=90.28).

The objective is to serve as a descriptive and educational report regarding the case of an eight-year-old spayed mixed-breed cat with nephrotic-range tubular and glomerular lesion, with no history of prior medication use or comorbidities, the main complaint being prostration and sudden weight gain. Physical examination revealed anasarca, moderate dyspnea and paradoxical breathing. Imaging tests revealed bicavitary effusion and subcutaneous edema. Laboratory analyses revealed serum creatinine equal to 3.0 mg/dL, severe hypoalbuminemia of 0.8g/dL, urine specific gravity equal to 1.020 and intense proteinuria (UPC ratio= 13.09). Urinary electrophoresis confirmed proteinuria with both glomerular and tubular involvement. This led to the suspicion of nephrotic syndrome with mixed-origin lesions. Treatment included furosemide, dexamethasone, benazepril, omega-3 fatty acid, mirtazapine and renal diet, in addition to procedures such as paracentesis for drainage. Progressive clinical improvement was observed, with resolution of anasarca by day 21, normalization of albumin by day 37 and a reduction of up to 93.85% in proteinuria nine months after the end of treatment. The patient remained stable, with no recurrence of symptoms. The therapeutic conclusions are limited by the single-case design, although continuous clinical and laboratory monitoring was implemented, aiming to adjust therapeutic management.

This study assessed the effect of high-fat food on pharmacokinetics and safety of amlodipine, benazepril, and benazeprilat in healthy Chinese participants under fasting and fed conditions from a bioequivalence trial. This trial enrolled a total of 92 healthy participants, and there was a significant difference in age between fasting and fed trials (P = .006). These participants received an amlodipine/benazepril capsule containing 5 mg amlodipine and 10 mg benazepril each period with a 21-day washout under fasting or fed conditions. Twenty-four blood samples were obtained from baseline to 168 h after drug administration for pharmacokinetic analyses. The plasma concentrations of amlodipine, benazepril, and benazeprilat were determined by a validated liquid chromatography-tandem mass spectrometry method. After controlling for age, analysis of covariance (ANCOVA) or Quade's ANCOVA of pharmacokinetic results indicated that a high-fat meal did not significantly influence the primary pharmacokinetic parameters of amlodipine, benazepril, and benazeprilat, except for the maximum plasma concentration (Cmax) and time to reach maximum plasma concentration (Tmax) for benazepril and benazeprilat. The high-fat food decreased Cmax of benazepril by 64.1% and Cmax of benazeprilat by 30.8%, and increased Tmax of benazepril by 408.2% and Tmax of benazeprilat by 167.8% The incidence of most frequently observed AE of hypotension was significantly different (P = .014, risk ratio = 2.286, and 95% confidence intervals 1.103 to 4.737) under fasting and fed conditions. It suggested that high-fat food containing 800 to 1000 kcal might be the risk factor for healthy Chinese participants taking amlodipine/benazepril capsules.