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Analysis of US Marketed Artemisinin Supplements for Use in Dogs. 美国市场上供犬使用的青蒿素补充剂分析。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-24 DOI: 10.1111/jvp.13480
Alyssa R Berman, Adam J Birkenheuer, Emily L Sorah, Mark G Papich

Oral artemisinin has antiparasitic activity and may help improve treatment success rates in dogs infected with Babesia gibsoni. However, these artemisinin products are unapproved and unregulated botanical supplements. They have not been evaluated for safety and efficacy or for strength, purity, or quality compared with a reference standard. Before considering these products for a clinical study, we evaluated the strength of four suppliers of artemisinin capsules using an high-performance liquid chromatography method validated in our laboratory. We found that the four artemisinin-labeled products that were tested had high within product and between product variability in capsule strength compared with the stated capsule strength on the product label. No products met the acceptance criteria of the United States Pharmacopeia and International Council for Harmonisation (ICH) as well as the criteria adapted by the authors. One product had no detectable artemisinin, and the other three products were much higher than the stated label strength. The results of this study reinforce the importance of testing unapproved and unregulated supplements before recommending a supplement for clinical use in dogs.

口服青蒿素具有抗寄生虫活性,可能有助于提高感染吉布森巴贝西亚原虫的狗的治疗成功率。不过,这些青蒿素产品是未经批准和监管的植物补充剂。与参考标准相比,它们的安全性和有效性或强度、纯度或质量均未经评估。在考虑将这些产品用于临床研究之前,我们使用实验室验证的高效液相色谱法对四家青蒿素胶囊供应商的青蒿素强度进行了评估。我们发现,与产品标签上标明的胶囊强度相比,接受测试的四种贴有青蒿素标签的产品在产品内部和产品之间的胶囊强度差异很大。没有一种产品符合美国药典和国际协调理事会(ICH)的验收标准以及作者调整的标准。其中一种产品检测不到青蒿素,另外三种产品的青蒿素含量远远高于标签上标明的含量。这项研究的结果强化了在推荐一种补充剂用于狗的临床治疗之前对未经批准和未受管制的补充剂进行检测的重要性。
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引用次数: 0
Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin in Nanyang Cattle. 南阳牛体内恩诺沙星及其代谢物环丙沙星的药代动力学。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-16 DOI: 10.1111/jvp.13478
Fang Yang, Long-Ji Sun, Fan Yang, Shi-Hao Li, Yu-Xin Chen, Wen-Rui Wang

The objective of this study was to determine the pharmacokinetics of enrofloxacin and its metabolite, ciprofloxacin, in Nanyang cattle after a single intravenous (IV), and intramuscular (IM) administration of enrofloxacin at 2.5 mg/kg body weight (BW). Blood samples were collected at predetermined time points. Enrofloxacin and ciprofloxacin concentrations in plasma were simultaneously determined using a high-performance liquid chromatography (HPLC) assay method and subjected to a non-compartmental analysis. After IV administration, enrofloxacin had a mean (±SD) volume of distribution at steady state (VSS) of 1.394 ± 0.349 L/kg, a terminal half-life (t1/2λz) of 3.592 ± 1.205 h, and a total body clearance (Cl) of 0.675 ± 0.16 L/h/kg. After IM administration, enrofloxacin was absorbed relatively slowly but completely, with a mean absorption time (MAT) of 6.051 ± 1.107 h and a bioavailability of 99.225 ± 7.389%. Both compounds were detected simultaneously in most plasma samples following both routes of administration, indicating efficient biotransformation of enrofloxacin to ciprofloxacin. After IV injection, the peak concentration (Cmax) of ciprofloxacin was 0.315 ± 0.017 μg/mL, observed at 0.958 ± 0.102 h. Following IM injection, the corresponding values were 0.071 ± 0.006 μg/mL and 3 ± 1.095 h, respectively. Following IV and IM administration, the conversion ratio of enrofloxacin to ciprofloxacin was calculated as 59.2 ± 9.6% and 31.2 ± 7.7%, respectively. The present results demonstrated favorable pharmacokinetic profiles for enrofloxacin, characterized by complete absorption with relatively slow kinetics, extensive distribution, efficient biotransformation to ciprofloxacin, and prolonged elimination in Nanyang cattle.

本研究的目的是测定南阳牛在一次静脉注射(IV)和肌肉注射(IM)2.5 毫克/千克体重的恩诺沙星后,恩诺沙星及其代谢物环丙沙星的药代动力学。在预定的时间点采集血液样本。采用高效液相色谱法同时测定血浆中恩诺沙星和环丙沙星的浓度,并进行非室分析。静脉给药后,恩诺沙星的平均(±SD)稳态分布容积(VSS)为 1.394 ± 0.349 L/kg,终末半衰期(t1/2λz)为 3.592 ± 1.205 h,全身清除率(Cl)为 0.675 ± 0.16 L/h/kg。用药后,恩诺沙星的吸收相对缓慢但完全,平均吸收时间(MAT)为 6.051 ± 1.107 h,生物利用度为 99.225 ± 7.389%。两种给药途径后的大多数血浆样本中都能同时检测到这两种化合物,这表明恩诺沙星能有效地生物转化为环丙沙星。静脉注射后,环丙沙星的峰值浓度(Cmax)为 0.315 ± 0.017 μg/mL,观察时间为 0.958 ± 0.102 h;IM 注射后,相应值分别为 0.071 ± 0.006 μg/mL和 3 ± 1.095 h。经计算,静脉注射和注射后,恩诺沙星与环丙沙星的转化率分别为 59.2 ± 9.6% 和 31.2 ± 7.7%。本研究结果表明,恩诺沙星在南阳牛体内具有良好的药代动力学特征,即吸收完全、动力学相对缓慢、分布广泛、高效生物转化为环丙沙星以及消除时间较长。
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引用次数: 0
The pharmacokinetics/pharmacodynamics integration of tilmicosin against Mycoplasma synoviae in vitro and in vivo. 替米考星对滑膜支原体的体外和体内药代动力学/药效学整合。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-12 DOI: 10.1111/jvp.13475
Xiu Yan, Jinxin Liu, Weihuo Li, Shuti Song, Zhaofeng Yao, Yixin Jia, Sheng Yuan, Hong Yang, Nan Zhang

Mycoplasma synoviae (MS) infection is a serious threat to poultry industry in China. Tilmicosin is a semisynthetic macrolide antibiotic used only in animals and has shown potential efficacy against MS, but there were no reported articles concerning the pharmacokinetics/pharmacodynamics (PK/PD) interactions of tilmicosin against MS in vitro and vivo. This study aimed to assess the antibacterial activity of tilmicosin against MS in vitro and in vivo using PK/PD model to provide maximal efficacy. The minimum inhibitory concentration (MIC) and killing rates of different drug concentrations were measured using the microdilution method in vitro. Then, tilmicosin was administered orally to the MS-infected chickens at doses of 7.5 and 60 mg/kg, and the PK parameters of tilmicosin in joint dialysates were determined using high-pressure liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) combined with the microdialysis technique. The antibacterial effect (△E) was calculated when the infected chickens were administered a single oral dose of tilmicosin at 4, 7.5, 15, 30, and 60 mg/kg b.w. The PK and PD data were fitted using the Sigmoid Emax model to evaluate the PK/PD interactions of tilmicosin against MS. The bactericidal activity of tilmicosin against MS was concentration dependent. Furthermore, the PK/PD index of AUC0-72h/MIC exhibited the most optimal fitting results (R2 = .98). The MS load decreased by 1, 2, and 3 Log10 CFU/mL, then AUC/MIC was determined as 13.99, 20.53, and 28.23 h, respectively, and the bactericidal effect can be achieved when the dose of MS-infected chickens is at 31.64 mg/kg b.w. The findings of this study hold significant implications for optimizing the treatment regimen for MS infection.

滑膜支原体(MS)感染严重威胁着中国的家禽业。替米考星是一种仅用于动物的半合成大环内酯类抗生素,对滑膜支原体感染有潜在疗效,但目前尚无关于替米考星在体外和体内对滑膜支原体感染的药代动力学/药效动力学(PK/PD)相互作用的报道。本研究旨在利用PK/PD模型评估替米考星在体外和体内对多发性硬化症的抗菌活性,以获得最大疗效。采用微量稀释法在体外测定了不同药物浓度的最低抑菌浓度(MIC)和杀灭率。采用高压液相色谱/串联质谱(HPLC-MS/MS)结合微透析技术测定了关节透析液中替米考星的PK参数。利用 Sigmoid Emax 模型对替米考星的 PK 和 PD 数据进行拟合,以评估替米考星对 MS 的 PK/PD 相互作用。替米考星对多发性硬化症的杀菌活性与浓度有关。此外,AUC0-72h/MIC的PK/PD指数显示出最理想的拟合结果(R2 = .98)。MS载量减少1、2和3 Log10 CFU/mL时,AUC/MIC分别为13.99、20.53和28.23 h,MS感染鸡的剂量为31.64 mg/kg体重时可达到杀菌效果。
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引用次数: 0
Assessment of Single-Dose Pharmacokinetics of Oxolinic Acid in Rainbow Trout and Determination of In Vitro Antibacterial Activity Against Pathogenic Bacteria From Diseased Fish. 评估 Oxolinic Acid 在虹鳟鱼体内的单剂量药代动力学,并确定其对病鱼致病菌的体外抗菌活性。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-09 DOI: 10.1111/jvp.13477
Richa Pathak, Sumanta Kumar Mallik, Prasanna Kumar Patil, Neetu Shahi, Krishna Kala, Raja Adil Hussain Bhat, Ranjit Kumar Nadella, Nityanand Pandey, Pramod Kumar Pandey

In response to the heightened risk of bacterial diseases in fish farms caused by increased demand for fish consumption and subsequent overcrowding, researchers are currently investigating the efficacy and residue management of oxolinic acid (OA) as a treatment for bacterial infections in fish. This research is crucial for gaining a comprehensive understanding of the pharmacokinetics of OA. The present study investigates pharmacokinetics of OA in juvenile rainbow trout. The fish were given a 12 mg kg-1 dose of OA through their feed, and tissue samples were collected of the liver, kidney, gill, intestine, muscle, and plasma for analysis using LC-MS/MS. The highest concentrations of the drug were found in the gill (4096.55 μg kg-1) and intestine (11592.98 μg kg-1), with significant absorption also seen in the liver (0.36 L/h) and gill (0.07 L/h) (p < 0.05). The liver (0.21 L/h) and kidney (0.03 L/h) were found to be the most efficient (p < 0.05) at eliminating the drug. The study also confirmed the drug antimicrobial effectiveness against several bacterial pathogens, including Shewanella xiamenensis (0.25 μg mL-1), Lactococcus garvieae (1 μg mL-1), and Chryseobacterium aquaticum (4 μg mL-1). The study concludes significant variations among different fish tissues, with higher concentrations and longer half-lives observed in the kidney and intestine. The lowest MIC value recorded against major bacterial pathogens demonstrated its therapeutic potential in aquaculture. It also emphasizes the importance of understanding OA pharmacokinetics to optimize antimicrobial therapy in aquaculture.

由于鱼类消费需求的增加以及随之而来的过度拥挤,鱼类养殖场中细菌性疾病的风险增加,为应对这种情况,研究人员目前正在研究氧喹啉酸(OA)作为治疗鱼类细菌感染的药物的功效和残留管理。这项研究对于全面了解 OA 的药代动力学至关重要。本研究调查了 OA 在幼年虹鳟鱼体内的药代动力学。研究人员通过饲料给虹鳟鱼喂食 12 mg kg-1 剂量的 OA,然后采集其肝、肾、鳃、肠、肌肉和血浆组织样本,使用 LC-MS/MS 进行分析。鳃(4096.55 μg kg-1)和肠(11592.98 μg kg-1)中的药物浓度最高,肝脏(0.36 升/小时)和鳃(0.07 升/小时)(p-1)、Lactococcus garvieae(1 μg mL-1)和 Chryseobacterium aquaticum(4 μg mL-1)中也有显著吸收。研究结果表明,不同鱼类组织之间存在明显差异,肾脏和肠道中的浓度较高,半衰期较长。针对主要细菌病原体记录到的最低 MIC 值证明了它在水产养殖中的治疗潜力。它还强调了了解 OA 药代动力学以优化水产养殖中抗菌治疗的重要性。
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引用次数: 0
Pharmacokinetics and Alterations in Glucose and Insulin Levels After a Single Dose of Canagliflozin in Healthy Icelandic Horses. 健康冰岛马单次服用 Canagliflozin 后的药代动力学以及葡萄糖和胰岛素水平的变化。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-07 DOI: 10.1111/jvp.13476
Peter Michanek, Johan Bröjer, Inger Lilliehöök, Cathrine T Fjordbakk, Minerva Löwgren, Mikael Hedeland, Jonas Bergquist, Carl Ekstrand

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor that has shown promising results as a drug for the treatment of insulin dysregulation in horses. Even though CFZ is used clinically, no pharmacokinetic data has previously been published. In this study, the pharmacokinetics of CFZ after administration of a single oral dose of 1.8 mg/kg in eight healthy Icelandic horses was examined. Additionally, the effect of treatment on glucose and insulin levels in response to a graded glucose infusion was investigated. Plasma samples for CFZ quantification were taken at 0, 0.33, 0.66, 1, 1.33, 1.66, 2, 2.33, 2.66, 3, 3.5, 4, 5, 6, 8, 12, 24, 32, and 48 h post administration. CFZ was quantified using UHPLC coupled to tandem quadrupole mass spectrometry (UHPLC-MS/MS). A non-compartmental analysis revealed key pharmacokinetic parameters, including a median Tmax of 7 h, a Cmax of 2350 ng/mL, and a t1/2Z of 28.5 h. CFZ treatment reduced glucose (AUCGLU, p = 0.001) and insulin (AUCINS, p = 0.04) response to a graded glucose infusion administered 5 h after treatment. This indicates a rapid onset of action following a single dose in healthy Icelandic horses. No obvious adverse effects related to the treatment were observed.

Canagliflozin(CFZ)是一种钠-葡萄糖共转运体-2抑制剂,作为一种治疗马匹胰岛素失调的药物,它已显示出良好的效果。尽管 CFZ 已在临床上使用,但此前尚未公布其药代动力学数据。在本研究中,我们对 8 匹健康冰岛马单次口服 1.8 毫克/千克 CFZ 后的药代动力学进行了研究。此外,还研究了治疗对葡萄糖和胰岛素水平的影响,以及对分级葡萄糖输注的反应。在给药后 0、0.33、0.66、1、1.33、1.66、2、2.33、2.66、3、3.5、4、5、6、8、12、24、32 和 48 小时采集血浆样本用于 CFZ 定量。采用超高效液相色谱-串联四极杆质谱法(UHPLC-MS/MS)对 CFZ 进行定量。非室分析显示了关键的药代动力学参数,包括中位 Tmax 为 7 小时,Cmax 为 2350 纳克/毫升,t1/2Z 为 28.5 小时。CFZ 治疗可降低治疗后 5 小时对分级葡萄糖输注的葡萄糖(AUCGLU,p = 0.001)和胰岛素(AUCINS,p = 0.04)反应。这表明在健康的冰岛马体内单次给药后可迅速起效。没有观察到与治疗相关的明显不良反应。
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引用次数: 0
Pharmacokinetics and pharmacodynamics of two in-feed chlortetracycline regimens provided to beef cattle. 肉牛两种饲用金霉素方案的药代动力学和药效学。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-22 DOI: 10.1111/jvp.13474
Alyssa R Toillion, Michael D Apley, Johann F Coetzee, Kushan Kompalage

Plasma chlortetracycline (CTC) concentration data were subjected to Monte Carlo simulation of area under the concentration curve (AUC) values related to bovine respiratory disease pathogen MIC distributions to evaluate target attainment rates. Crossbred Hereford heifers were randomly assigned into two treatment groups. Treatment group (A) received chlortetracycline (CTC) at a target dose of 22 mg/kg of bodyweight daily for 5 consecutive days (n = 8) and group (B) received CTC at 350 mg/head per day (1.5 ± 0.2 mg/kg based on actual bodyweights) for seven consecutive days (n = 8). Non-compartmental analysis was used to calculate plasma-free drug CTC area under the concentration curves. The mean observed (±SD) free drug AUC values were 4.18 (±1.72) μg × h/mL and 0.30 (±0.06) μg × h/mL for treatment groups A and B, respectively. The probability of target attainment for AUC24/MIC values of 25 and 12.5 was modeled using Monte Carlo simulations. Treatment group A achieved >90% target attainment (AUC24/MIC of 25) at an MIC of 0.06 μg/mL, whereas treatment group B displayed only 12.6% target attainment (AUC24/MIC of 12.5) at the lowest MIC evaluated (0.015 μg/mL). Both in-feed CTC regimens failed to obtain a reasonable target attainment rate in light of expected MIC distributions of potential pathogens.

对血浆金霉素(CTC)浓度数据进行蒙特卡罗模拟,计算与牛呼吸道疾病病原体 MIC 分布相关的浓度曲线下面积(AUC)值,以评估目标达成率。杂交赫里福德小母牛被随机分配到两个治疗组。治疗组(A)每天按 22 毫克/千克体重的目标剂量连续 5 天服用金霉素(CTC)(n = 8),治疗组(B)每天按 350 毫克/头(根据实际体重计算为 1.5 ± 0.2 毫克/千克)的剂量连续 7 天服用金霉素(CTC)(n = 8)。采用非室分析法计算无血浆药物四氯化碳浓度曲线下的面积。治疗组 A 和 B 的游离药物 AUC 平均观察值(±SD)分别为 4.18 (±1.72) μg × h/mL 和 0.30 (±0.06) μg × h/mL。AUC24/MIC 值为 25 和 12.5 时的达标概率是通过蒙特卡罗模拟计算得出的。当 MIC 值为 0.06 μg/mL 时,治疗组 A 的达标率大于 90%(AUC24/MIC 值为 25),而治疗组 B 在最低 MIC 值(0.015 μg/mL)下的达标率仅为 12.6%(AUC24/MIC 值为 12.5)。考虑到潜在病原体的预期 MIC 分布,两种喂入 CTC 方案都未能获得合理的目标达标率。
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引用次数: 0
Single intravenous and oral dose pharmacokinetics of the antiseizure medication brivaracetam in healthy cats. 在健康猫体内单次静脉注射和口服抗癫痫药物布瓦西坦的药代动力学。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-17 DOI: 10.1111/jvp.13473
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.

经证实对猫有疗效的抗癫痫药物数量有限。因此,有必要对较新药物的药代动力学进行评估,以便制定适当的用药方案。布里瓦西坦(Brivaracetam,BRV)是左乙拉西坦的一种药效更强的类似物,已被美国食品药品管理局批准用于人类。本研究的目的是描述健康猫静脉注射和口服 BRV 的药代动力学。这项交叉研究涉及 8 只健康猫,分别在空腹状态下静脉注射和口服 10 毫克 BRV。采用液相色谱-质谱法进行分析。对数据进行了非室分析。最大浓度中值(最小-最大)、达到最大浓度的时间、曲线下面积、消除半衰期和口服绝对生物利用度分别为 902(682-1036)纳克/毫升、0.6(0.5-2.0)小时、6.4(5.2-7.2)小时、8145(6669-9351)纳克×小时/毫升和 100%(85-110)。所有猫都能很好地耐受 BRV。口服和静脉注射单剂量 BRV 的耐受性都很好。最大浓度的产生速度很快,且在被认为具有治疗作用的人类参考区间内。
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引用次数: 0
Comparative pharmacokinetics of a single oral dose of meloxicam in the California sea lion (Zalophus californianus) and Pacific harbor seal (Phoca vitulina richardii). 加州海狮(Zalophus californianus)和太平洋海豹(Phoca vitulina richardii)单次口服美洛昔康的药代动力学比较。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-14 DOI: 10.1111/jvp.13469
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.

药代动力学研究调查了美洛昔康(一种非甾体类消炎药)在多种非家养动物中的剂量策略;但是,此前还没有研究调查过针对针鱼的有充分依据的剂量。要制定给药方案,就需要药代动力学信息,并研究不同种类的松狮之间的差异。显然,健康的加州海狮(Zalophus californianus: CSL; n = 13)和太平洋港海豹(Phoca vitulina richardii: PHS; n = 17)已完成康复,它们被纳入了一项基于群体的药代动力学研究。每只动物口服一次 0.1 毫克/千克的美洛昔康,在 96 小时的研究期间,每只动物在不同时间间隔采集两次血液样本。通过高压液相色谱法测定血浆中的美洛昔康浓度。数据采用非线性混合效应模型(Phoenix® NLME™, Certara, St.)结果表明,在 PHS 中,血浆峰浓度(Cmax)为 0.33 μg/mL,消除半衰期(Ke t½ )为 31.53 h;在 CSL 中,Cmax 为 0.17 μg/mL,Ke t½ 为 32.71 h。消除半衰期长于之前推荐的针鼹鼠用药时间间隔;但是,我们无法根据这些结果推测最佳临床剂量。
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引用次数: 0
Sodium glucose transporter 2 inhibitors: Will these drugs benefit non-diabetic veterinary patients with cardiac and kidney diseases? 钠葡萄糖转运体 2 抑制剂:这些药物对患有心脏和肾脏疾病的非糖尿病兽医患者有益吗?
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-13 DOI: 10.1111/jvp.13472
Jonathan Elliott, Mark A Oyama

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.

钠葡萄糖转运体 2 型(SGLT2)抑制剂已被引入人类医疗领域,其有益效果超出了预期的血糖控制改善。这些药物似乎不仅能防止糖尿病患者的心血管疾病和肾脏疾病恶化,还能防止非糖尿病人类患者的心血管疾病和肾脏疾病恶化。由于这些药物已获得用于糖尿病猫的有条件批准,并正被用于其他兽医物种,人们提出了一个耐人寻味的问题:这些药物是否会对猫狗产生类似的心血管和肾脏保护作用?SGLT2 抑制剂具有心血管和肾脏保护作用的主要机制仍未完全确定。本文从猫狗进行性心血管疾病和肾脏疾病的病理生理学角度回顾了这些机制,旨在预测这些药物对哪类非糖尿病兽医患者最有益。
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引用次数: 0
Sodium-glucose transport protein 2 inhibitor use in the management of insulin dysregulation in ponies and horses. 钠-葡萄糖转运蛋白 2 抑制剂用于治疗小马和马的胰岛素失调。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-10 DOI: 10.1111/jvp.13470
Nicola J Menzies-Gow, Edward J Knowles

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。
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Journal of veterinary pharmacology and therapeutics
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