Tom Jukier, Chu Zhang, Robert D. Arnold, Amanda Gross
The number of available antiseizure medications with demonstrated efficacy in cats is limited. As such, there is a need to evaluate the pharmacokinetics of newer medications so that proper dosing regimens can be made. Brivaracetam (BRV) is a more potent analogue of levetiracetam, and is Food and Drug Administration approved for use in people. The goal of this study was to describe the pharmacokinetics of intravenous and oral doses of BRV in healthy cats. A cross-over study involving eight healthy cats, that were administered 10 mg of BRV intravenously as a bolus and orally in the fasted state. Blood samples were collected over 24 h. Analysis was performed using liquid chromatography-mass spectrometry. Data were subjected to non-compartmental analysis. Median (min–max) of maximal concentration, time to maximal concentration, area under the curve, elimination half-life and oral absolute bioavailability were 902 (682–1036) ng/mL, 0.6 (0.5–2.0) h, 6.4 (5.2–7.2) h, 8145 (6669–9351) ng × h/mL and 100% (85–110) respectively. BRV appeared to be well tolerated by all cats. A single dose of BRV is well tolerated both orally and intravenously. Maximal concentrations are produced rapidly and within the human reference interval considered to be therapeutic.
{"title":"Single intravenous and oral dose pharmacokinetics of the antiseizure medication brivaracetam in healthy cats","authors":"Tom Jukier, Chu Zhang, Robert D. Arnold, Amanda Gross","doi":"10.1111/jvp.13473","DOIUrl":"10.1111/jvp.13473","url":null,"abstract":"<p>The number of available antiseizure medications with demonstrated efficacy in cats is limited. As such, there is a need to evaluate the pharmacokinetics of newer medications so that proper dosing regimens can be made. Brivaracetam (BRV) is a more potent analogue of levetiracetam, and is Food and Drug Administration approved for use in people. The goal of this study was to describe the pharmacokinetics of intravenous and oral doses of BRV in healthy cats. A cross-over study involving eight healthy cats, that were administered 10 mg of BRV intravenously as a bolus and orally in the fasted state. Blood samples were collected over 24 h. Analysis was performed using liquid chromatography-mass spectrometry. Data were subjected to non-compartmental analysis. Median (min–max) of maximal concentration, time to maximal concentration, area under the curve, elimination half-life and oral absolute bioavailability were 902 (682–1036) ng/mL, 0.6 (0.5–2.0) h, 6.4 (5.2–7.2) h, 8145 (6669–9351) ng × h/mL and 100% (85–110) respectively. BRV appeared to be well tolerated by all cats. A single dose of BRV is well tolerated both orally and intravenously. Maximal concentrations are produced rapidly and within the human reference interval considered to be therapeutic.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 6","pages":"461-468"},"PeriodicalIF":1.5,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emily J. Trumbull, Mark G. Papich, Mattison Peters, Emily R. Whitmer, Michelle Rivard, Cara L. Field
Pharmacokinetics studies have investigated meloxicam, a non-steroidal anti-inflammatory drug, dosing strategies in a wide variety of non-domestic animals; however, there is no prior study examining well-founded dosing for pinnipeds. To develop dosing protocols, pharmacokinetic information is needed, with an examination of differences between pinniped species. Apparently, healthy California sea lions (Zalophus californianus: CSL; n = 13) and Pacific harbor seals (Phoca vitulina richardii: PHS; n = 17) that had completed rehabilitation were enrolled into a population-based pharmacokinetic study. Each animal was administered a single oral dose of meloxicam at 0.1 mg/kg, and two blood samples were collected from each animal at varying intervals during a 96-h study period. Plasma concentrations of meloxicam were determined by high-pressure liquid chromatography. Data were analyzed with nonlinear mixed effects modeling (Phoenix® NLME™, Certara, St. Louis, MO 63105, USA). The results indicated that in PHS, peak plasma concentration (Cmax) was 0.33 μg/mL with an elimination half-life (Ke t½) of 31.53 h. In CSL, Cmax was 0.17 μg/mL with Ke t½ of 32.71 h. All animals enrolled completed the study without outward adverse clinical signs. The elimination half-life was longer than previously recommended dosing intervals for pinnipeds; however, we cannot speculate in the optimum clinical dose from these results.
{"title":"Comparative pharmacokinetics of a single oral dose of meloxicam in the California sea lion (Zalophus californianus) and Pacific harbor seal (Phoca vitulina richardii)","authors":"Emily J. Trumbull, Mark G. Papich, Mattison Peters, Emily R. Whitmer, Michelle Rivard, Cara L. Field","doi":"10.1111/jvp.13469","DOIUrl":"10.1111/jvp.13469","url":null,"abstract":"<p>Pharmacokinetics studies have investigated meloxicam, a non-steroidal anti-inflammatory drug, dosing strategies in a wide variety of non-domestic animals; however, there is no prior study examining well-founded dosing for pinnipeds. To develop dosing protocols, pharmacokinetic information is needed, with an examination of differences between pinniped species. Apparently, healthy California sea lions (<i>Zalophus californianus</i>: CSL; <i>n</i> = 13) and Pacific harbor seals (<i>Phoca vitulina richardii</i>: PHS; <i>n</i> = 17) that had completed rehabilitation were enrolled into a population-based pharmacokinetic study. Each animal was administered a single oral dose of meloxicam at 0.1 mg/kg, and two blood samples were collected from each animal at varying intervals during a 96-h study period. Plasma concentrations of meloxicam were determined by high-pressure liquid chromatography. Data were analyzed with nonlinear mixed effects modeling (Phoenix® NLME™, Certara, St. Louis, MO 63105, USA). The results indicated that in PHS, peak plasma concentration (C<sub>max</sub>) was 0.33 μg/mL with an elimination half-life (K<sub>e</sub> t½) of 31.53 h. In CSL, C<sub>max</sub> was 0.17 μg/mL with K<sub>e</sub> t½ of 32.71 h. All animals enrolled completed the study without outward adverse clinical signs. The elimination half-life was longer than previously recommended dosing intervals for pinnipeds; however, we cannot speculate in the optimum clinical dose from these results.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 6","pages":"485-491"},"PeriodicalIF":1.5,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13469","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sodium glucose transporter type 2 (SGLT2) inhibitors have been introduced into human medicine where their beneficial effects go beyond the expected improvement in blood glucose control. These drugs appear to prevent progression of both cardiovascular and kidney diseases, not only in diabetic but also in non-diabetic human patients. As these drugs have received conditional approval for use in diabetic cats and are being used in other veterinary species, the intriguing question as to whether they will have similar cardioprotective and nephroprotective effects in dogs and cats is being asked. The primary mechanism(s) by which SGLT2 inhibitors are cardio- and nephroprotective remain to be fully characterized. This paper reviews these suggested mechanisms in the context of the pathophysiology of progressive cardiovascular and kidney diseases in dogs and cats with the goal of predicting which categories of non-diabetic veterinary patients these drugs might be of most benefit.
{"title":"Sodium glucose transporter 2 inhibitors: Will these drugs benefit non-diabetic veterinary patients with cardiac and kidney diseases?","authors":"Jonathan Elliott, Mark A Oyama","doi":"10.1111/jvp.13472","DOIUrl":"https://doi.org/10.1111/jvp.13472","url":null,"abstract":"<p><p>Sodium glucose transporter type 2 (SGLT2) inhibitors have been introduced into human medicine where their beneficial effects go beyond the expected improvement in blood glucose control. These drugs appear to prevent progression of both cardiovascular and kidney diseases, not only in diabetic but also in non-diabetic human patients. As these drugs have received conditional approval for use in diabetic cats and are being used in other veterinary species, the intriguing question as to whether they will have similar cardioprotective and nephroprotective effects in dogs and cats is being asked. The primary mechanism(s) by which SGLT2 inhibitors are cardio- and nephroprotective remain to be fully characterized. This paper reviews these suggested mechanisms in the context of the pathophysiology of progressive cardiovascular and kidney diseases in dogs and cats with the goal of predicting which categories of non-diabetic veterinary patients these drugs might be of most benefit.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laminitis is a common and painful condition of the equine foot and approximately 90% of cases are associated with insulin dysregulation (ID) that is a central feature of the common endocrine disorder equine metabolic syndrome (EMS) and occurs in a subset of animals with pituitary pars intermedia dysfunction. Additional features of EMS include obesity, altered circulating concentrations of adipokines (particularly adiponectin and leptin) and hypertriglyceridaemia. Obesity, ID, hypoadiponectinaemia, hyperleptinaemia and an altered plasma lipid profile are also features of human metabolic syndrome (HMS) alongside hyperglycaemia. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel class of oral hypoglycaemic agents used in combination with lifestyle changes in the management of HMS. SGLT2 receptors are responsible for 90% of the renal glucose reabsorption that occurs in the proximal convoluted tubule. Thus, these drugs increase urinary glucose excretion by suppressing glucose reabsorption from the glomerular filtrate resulting in urinary calorie loss with consequent weight loss and improvements in ID, hyperglycemia, hypoadiponectinaemia and hyperleptinaemia. There are no licenced veterinary drugs available for treating ID and preventing insulin-associated laminitis in horses. Thus, the use of SGLT2i for the control of equine hyperinsulinaemia with the goal of improving recovery from associated active laminitis or preventing future laminitis has recently been advocated. There are a small number of published studies reporting the use of the SGLT2i canagliflozin, ertugliflozin and velagliflozin to aid the management of equine ID. However, the doses used are largely extrapolated from human studies with limited consideration of species-specific variations. In addition, there is limited evaluation of the fundamental differences between ID in horses and humans, particularly the fact that most horses with ID remain hyperinsulinaemic but normoglycaemic such that increased urinary loss of glucose may not explain the beneficial effects of these drugs. Further study of the potential deleterious effects of treatment-associated hypertriglyceridaemia is required together with the effect of SGLT2i therapy on circulating concentrations of adipokines in horses.
蹄叶炎是马蹄部常见的一种疼痛症状,约 90% 的病例与胰岛素失调 (ID) 有关,而胰岛素失调是常见的内分泌失调性疾病马代谢综合征 (EMS) 的一个核心特征,发生在垂体中叶旁功能障碍的动物中。EMS 的其他特征还包括肥胖、脂肪因子(尤其是脂肪连素和瘦素)循环浓度改变和高甘油三酯血症。肥胖、ID、低脂联素血症、高瘦素血症和血浆脂质谱改变也是人类代谢综合征(HMS)的特征,此外还有高血糖。钠-葡萄糖共转运体 2 抑制剂(SGLT2i)是一类新型口服降糖药,在治疗 HMS 的过程中与改变生活方式相结合使用。SGLT2 受体负责近端曲小管中 90% 的肾葡萄糖重吸收。因此,这些药物通过抑制肾小球滤液对葡萄糖的重吸收来增加尿糖排泄,从而减少尿中热量,进而减轻体重,改善 ID、高血糖、低脂血和高瘦血症。目前还没有获得许可的兽药可用于治疗 ID 和预防马匹胰岛素相关性蹄叶炎。因此,最近有人主张使用 SGLT2i 来控制马的高胰岛素血症,以改善相关活动性蹄叶炎的恢复或预防未来的蹄叶炎。有少量已发表的研究报告称,SGLT2i Canagliflozin、ertugliflozin 和 velagliflozin 可用于辅助治疗马匹 ID。然而,所使用的剂量大多是从人类研究中推断出来的,对物种的特异性差异考虑有限。此外,对马匹和人类 ID 基本差异的评估也很有限,特别是大多数患有 ID 的马匹仍然存在高胰岛素血症,但血糖正常,因此尿液中葡萄糖流失的增加可能无法解释这些药物的有益作用。需要进一步研究治疗相关高甘油三酯血症的潜在有害影响,以及 SGLT2i 疗法对马体内脂肪因子循环浓度的影响。
{"title":"Sodium-glucose transport protein 2 inhibitor use in the management of insulin dysregulation in ponies and horses.","authors":"Nicola J Menzies-Gow, Edward J Knowles","doi":"10.1111/jvp.13470","DOIUrl":"https://doi.org/10.1111/jvp.13470","url":null,"abstract":"<p><p>Laminitis is a common and painful condition of the equine foot and approximately 90% of cases are associated with insulin dysregulation (ID) that is a central feature of the common endocrine disorder equine metabolic syndrome (EMS) and occurs in a subset of animals with pituitary pars intermedia dysfunction. Additional features of EMS include obesity, altered circulating concentrations of adipokines (particularly adiponectin and leptin) and hypertriglyceridaemia. Obesity, ID, hypoadiponectinaemia, hyperleptinaemia and an altered plasma lipid profile are also features of human metabolic syndrome (HMS) alongside hyperglycaemia. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel class of oral hypoglycaemic agents used in combination with lifestyle changes in the management of HMS. SGLT2 receptors are responsible for 90% of the renal glucose reabsorption that occurs in the proximal convoluted tubule. Thus, these drugs increase urinary glucose excretion by suppressing glucose reabsorption from the glomerular filtrate resulting in urinary calorie loss with consequent weight loss and improvements in ID, hyperglycemia, hypoadiponectinaemia and hyperleptinaemia. There are no licenced veterinary drugs available for treating ID and preventing insulin-associated laminitis in horses. Thus, the use of SGLT2i for the control of equine hyperinsulinaemia with the goal of improving recovery from associated active laminitis or preventing future laminitis has recently been advocated. There are a small number of published studies reporting the use of the SGLT2i canagliflozin, ertugliflozin and velagliflozin to aid the management of equine ID. However, the doses used are largely extrapolated from human studies with limited consideration of species-specific variations. In addition, there is limited evaluation of the fundamental differences between ID in horses and humans, particularly the fact that most horses with ID remain hyperinsulinaemic but normoglycaemic such that increased urinary loss of glucose may not explain the beneficial effects of these drugs. Further study of the potential deleterious effects of treatment-associated hypertriglyceridaemia is required together with the effect of SGLT2i therapy on circulating concentrations of adipokines in horses.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The pharmacokinetics and residue depletion of doxycycline (DOX) in striped catfish (Pagasianodon hypophthalmus) after oral dosage were investigated. The pharmacokinetic experiment was conducted in an aquarium, while the experiment of residue depletion was performed in both an aquarium and earth ponds. Medicated feed was administered orally using the gavage method at a dosage of 20 mg/kg body weight. Blood, liver, and kidney from medicated fish samples were collected. In the depletion experiments, fish were fed medicated feed for five consecutive days at a dosage of 20 mg/kg body weight, with samples collected during and after medication. The concentrations of DOX were quantified using an LC-MS/MS system. The pharmacokinetics parameters of DOX in striped catfish included the absorption rate constant (ka), absorption half-life (T1/2abs), maximal plasma concentration (Cmax), time to maximal plasma concentration (Tmax), and area under the plasma concentration-time curve from time 0 to 96 h (AUC0-96 h) which were 0.12 h-1, 5.68 h, 1123.45 ng/mL, 8.19 h, and 25,018 ng/mL/h, respectively. Residue depletion results indicated that the withdrawal times of DOX in muscle (with skin) from fish kept in the aquarium were slightly longer than that in fish raised in earth ponds, corresponding to 194 degree-days compared with 150 degree-days. In conclusion, administration of DOX at the dosage of 20 mg/kg body weight can be used for treatment of bacterial infections in striped catfish, and a withdrawal time of 5 days at 29.4°C will ensure consumer food safety due to the rapid depletion of DOX from muscle and skin.
{"title":"Doxycycline pharmacokinetics and tissue depletion in striped catfish (Pagasianodon hypophthalmus) after oral administration.","authors":"Pham Quang Vinh, Nguyen Quoc Thinh, Mathias Devreese, Siska Croubels, Dang Thi Hoang Oanh, Anders Dalsgaard, Masashi Maita, Tran Minh Phu","doi":"10.1111/jvp.13471","DOIUrl":"https://doi.org/10.1111/jvp.13471","url":null,"abstract":"<p><p>The pharmacokinetics and residue depletion of doxycycline (DOX) in striped catfish (Pagasianodon hypophthalmus) after oral dosage were investigated. The pharmacokinetic experiment was conducted in an aquarium, while the experiment of residue depletion was performed in both an aquarium and earth ponds. Medicated feed was administered orally using the gavage method at a dosage of 20 mg/kg body weight. Blood, liver, and kidney from medicated fish samples were collected. In the depletion experiments, fish were fed medicated feed for five consecutive days at a dosage of 20 mg/kg body weight, with samples collected during and after medication. The concentrations of DOX were quantified using an LC-MS/MS system. The pharmacokinetics parameters of DOX in striped catfish included the absorption rate constant (k<sub>a</sub>), absorption half-life (T<sub>1/2abs</sub>), maximal plasma concentration (C<sub>max</sub>), time to maximal plasma concentration (T<sub>max</sub>), and area under the plasma concentration-time curve from time 0 to 96 h (AUC<sub>0-96 h</sub>) which were 0.12 h<sup>-1</sup>, 5.68 h, 1123.45 ng/mL, 8.19 h, and 25,018 ng/mL/h, respectively. Residue depletion results indicated that the withdrawal times of DOX in muscle (with skin) from fish kept in the aquarium were slightly longer than that in fish raised in earth ponds, corresponding to 194 degree-days compared with 150 degree-days. In conclusion, administration of DOX at the dosage of 20 mg/kg body weight can be used for treatment of bacterial infections in striped catfish, and a withdrawal time of 5 days at 29.4°C will ensure consumer food safety due to the rapid depletion of DOX from muscle and skin.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are routinely used in the management of human type 2 diabetes and have been shown to effectively mitigate hyperglycemia and reduce the risks of cardiovascular and renal compromise. Two SGLT2 inhibitors, namely bexagliflozin and velagliflozin, were recently FDA approved for the treatment of uncomplicated feline diabetes mellitus. These oral hypoglycemic agents are a suitable option for many newly diagnosed cats, with rapid improvements in glycemic control and clinical signs. Suitable candidates must have some residual β-cell function, as some endogenous insulin production is required to prevent ketosis. Appropriate patient selection and monitoring are necessary, and practitioners should be aware of serious complications such as euglycemic diabetic ketoacidosis.
{"title":"SGLT2 inhibitor use in the management of feline diabetes mellitus.","authors":"Audrey K Cook, Ellen Behrend","doi":"10.1111/jvp.13466","DOIUrl":"https://doi.org/10.1111/jvp.13466","url":null,"abstract":"<p><p>Sodium-glucose cotransporter-2 (SGLT2) inhibitors are routinely used in the management of human type 2 diabetes and have been shown to effectively mitigate hyperglycemia and reduce the risks of cardiovascular and renal compromise. Two SGLT2 inhibitors, namely bexagliflozin and velagliflozin, were recently FDA approved for the treatment of uncomplicated feline diabetes mellitus. These oral hypoglycemic agents are a suitable option for many newly diagnosed cats, with rapid improvements in glycemic control and clinical signs. Suitable candidates must have some residual β-cell function, as some endogenous insulin production is required to prevent ketosis. Appropriate patient selection and monitoring are necessary, and practitioners should be aware of serious complications such as euglycemic diabetic ketoacidosis.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The phenomenon of predatory journals and awareness among researchers in veterinary medicine: Correspondence","authors":"Hineptch Daungsupawong, Viroj Wiwanitkit","doi":"10.1111/jvp.13468","DOIUrl":"10.1111/jvp.13468","url":null,"abstract":"","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 5","pages":"444-445"},"PeriodicalIF":1.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jessica D. Garcia, Joe S. Smith, David Minich, Makenna Hopson, Rebecca Rahn, Chiara Hampton, Meggan Graves, Geneviève Bussières, Pierre-Yves Mulon, Lisa S. Ebner, Sherry Cox
The purpose of this study was to evaluate the pharmacokinetics (PK) of intravenously (IV) and subcutaneously (SC) administered nalbuphine in domestic goats. Nalbuphine hydrochloride was administered at 0.8 mg/kg for both IV and SC routes in six goats with a minimum of 10-day washout period between sample collection phases. Eighteen plasma samples were collected over a 36-hour period, analyzed using reverse phase high-performance liquid chromatography (HPLC). Plasma data were analyzed using compartmental and noncompartmental approaches. Following IV nalbuphine administration, elimination half-life, area under the plasma concentration time curve from time 0 to infinity (AUC0 − ∞), concentration at time zero (C0), and total body clearance were 120.4 ± 39.1 (min−1 ± SD), 17311.01 ± 7227.32 (min·ng·mL−1 ± SD), 675.6 ± 337.13 (ng·mL−1 ± SD), and 44.5 ± 13.8 (mL·min−1·kg−1 ± SD), respectively. After SC nalbuphine administration, elimination half-life, area under the plasma concentration time curve from time 0 to infinity (AUC0 − ∞), and maximum plasma drug concentration were 129 ± 52.9 (min−1 ± SD), 20826.5 ± 14376.2 (min·ng·mL−1), and 368.03 ± 503.78 (ng·mL−1). Calculated bioavailability for the SC route was 138 ± 126 (% ± SD). Nalbuphine in goats is characterized by rapid elimination and high subcutaneous bioavailability and may be a safe analgesic opioid option in goats in the future.
{"title":"Pharmacokinetics of nalbuphine administered intravenously and subcutaneously in goats (Capra aegagrus hircus)","authors":"Jessica D. Garcia, Joe S. Smith, David Minich, Makenna Hopson, Rebecca Rahn, Chiara Hampton, Meggan Graves, Geneviève Bussières, Pierre-Yves Mulon, Lisa S. Ebner, Sherry Cox","doi":"10.1111/jvp.13463","DOIUrl":"10.1111/jvp.13463","url":null,"abstract":"<p>The purpose of this study was to evaluate the pharmacokinetics (PK) of intravenously (IV) and subcutaneously (SC) administered nalbuphine in domestic goats. Nalbuphine hydrochloride was administered at 0.8 mg/kg for both IV and SC routes in six goats with a minimum of 10-day washout period between sample collection phases. Eighteen plasma samples were collected over a 36-hour period, analyzed using reverse phase high-performance liquid chromatography (HPLC). Plasma data were analyzed using compartmental and noncompartmental approaches. Following IV nalbuphine administration, elimination half-life, area under the plasma concentration time curve from time 0 to infinity (AUC0 − ∞), concentration at time zero (<i>C</i><sub>0</sub>), and total body clearance were 120.4 ± 39.1 (min<sup>−1</sup> ± SD), 17311.01 ± 7227.32 (min·ng·mL<sup>−1</sup> ± SD), 675.6 ± 337.13 (ng·mL<sup>−1</sup> ± SD), and 44.5 ± 13.8 (mL·min<sup>−1</sup>·kg<sup>−1</sup> ± SD), respectively. After SC nalbuphine administration, elimination half-life, area under the plasma concentration time curve from time 0 to infinity (AUC0 − ∞), and maximum plasma drug concentration were 129 ± 52.9 (min<sup>−1</sup> ± SD), 20826.5 ± 14376.2 (min·ng·mL<sup>−1</sup>), and 368.03 ± 503.78 (ng·mL<sup>−1</sup>). Calculated bioavailability for the SC route was 138 ± 126 (% ± SD). Nalbuphine in goats is characterized by rapid elimination and high subcutaneous bioavailability and may be a safe analgesic opioid option in goats in the future.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 6","pages":"478-484"},"PeriodicalIF":1.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrea J. Gonzales, Michelle Aleo, Sean Mahabir, James Messamore, Michael Stegemann
Oclacitinib is a novel Janus kinase (JAK) inhibitor that potently inhibits JAK1-dependent cytokines involved in allergy, inflammation, and pruritus (IL-2, IL-4, IL-6, IL-13, and IL-31). Oclacitinib (Apoquel®, Zoetis Inc, Parsippany, NJ) is approved for the treatment/control of pruritus associated with allergic dermatitis and treatment/control of clinical manifestations of atopic dermatitis in dogs at least 12 months of age. To evaluate the effectiveness of oclacitinib in dogs with flea allergy dermatitis, the JAK1 selective inhibitor was tested in a placebo-controlled, masked, single-dose (0.4 mg/kg) or repeat-dose (0.4 mg/kg, twice daily for 2 weeks) study. Pruritic behaviors were quantitated by video recording, and erythema and skin lesions were assessed using a 10-cm visual analog scale (VAS). Results showed that oclacitinib reduced pruritus by 61% as early as 1.5 h after a single oral dose compared to placebo, with an average reduction (compared to placebo) of 85% 1–5 h after dosing (0.4 mg/kg; p < .0001). Oclacitinib also significantly reduced erythema (p < .0001) and skin lesion (p < .0005) VAS scores on Day 14 compared to placebo in a repeat dose study. No adverse events were noted during the conduct of these studies. IL-31 concentrations were elevated in the majority of dogs after flea infestation, suggesting JAK1-dependent cytokines may drive clinical signs of flea allergy dermatitis. These findings show that oclacitinib, an inhibitor of JAK1-dependent cytokines involved in allergy and inflammation can rapidly reduce clinical signs associated with flea allergic dermatitis in dogs.
{"title":"Oclacitinib (APOQUEL®) is a selective Janus kinase 1 inhibitor with efficacy in a canine model of flea allergic dermatitis","authors":"Andrea J. Gonzales, Michelle Aleo, Sean Mahabir, James Messamore, Michael Stegemann","doi":"10.1111/jvp.13462","DOIUrl":"10.1111/jvp.13462","url":null,"abstract":"<p>Oclacitinib is a novel Janus kinase (JAK) inhibitor that potently inhibits JAK1-dependent cytokines involved in allergy, inflammation, and pruritus (IL-2, IL-4, IL-6, IL-13, and IL-31). Oclacitinib (Apoquel®, Zoetis Inc, Parsippany, NJ) is approved for the treatment/control of pruritus associated with allergic dermatitis and treatment/control of clinical manifestations of atopic dermatitis in dogs at least 12 months of age. To evaluate the effectiveness of oclacitinib in dogs with flea allergy dermatitis, the JAK1 selective inhibitor was tested in a placebo-controlled, masked, single-dose (0.4 mg/kg) or repeat-dose (0.4 mg/kg, twice daily for 2 weeks) study. Pruritic behaviors were quantitated by video recording, and erythema and skin lesions were assessed using a 10-cm visual analog scale (VAS). Results showed that oclacitinib reduced pruritus by 61% as early as 1.5 h after a single oral dose compared to placebo, with an average reduction (compared to placebo) of 85% 1–5 h after dosing (0.4 mg/kg; <i>p</i> < .0001). Oclacitinib also significantly reduced erythema (<i>p</i> < .0001) and skin lesion (<i>p</i> < .0005) VAS scores on Day 14 compared to placebo in a repeat dose study. No adverse events were noted during the conduct of these studies. IL-31 concentrations were elevated in the majority of dogs after flea infestation, suggesting JAK1-dependent cytokines may drive clinical signs of flea allergy dermatitis. These findings show that oclacitinib, an inhibitor of JAK1-dependent cytokines involved in allergy and inflammation can rapidly reduce clinical signs associated with flea allergic dermatitis in dogs.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 6","pages":"447-453"},"PeriodicalIF":1.5,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Is it time to stop teaching pharmacology and focus on treatment planning instead?","authors":"Martin Hawes, Virginia Fajt, Arno Werners","doi":"10.1111/jvp.13467","DOIUrl":"10.1111/jvp.13467","url":null,"abstract":"","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 5","pages":"442-443"},"PeriodicalIF":1.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}