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.
{"title":"Analysis of US Marketed Artemisinin Supplements for Use in Dogs.","authors":"Alyssa R Berman, Adam J Birkenheuer, Emily L Sorah, Mark G Papich","doi":"10.1111/jvp.13480","DOIUrl":"https://doi.org/10.1111/jvp.13480","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046854","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}
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.
{"title":"Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin in Nanyang Cattle.","authors":"Fang Yang, Long-Ji Sun, Fan Yang, Shi-Hao Li, Yu-Xin Chen, Wen-Rui Wang","doi":"10.1111/jvp.13478","DOIUrl":"https://doi.org/10.1111/jvp.13478","url":null,"abstract":"<p><p>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 (V<sub>SS</sub>) of 1.394 ± 0.349 L/kg, a terminal half-life (t<sub>1/2λz</sub>) 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 (C<sub>max</sub>) 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.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988292","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}
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.
{"title":"The pharmacokinetics/pharmacodynamics integration of tilmicosin against Mycoplasma synoviae in vitro and in vivo.","authors":"Xiu Yan, Jinxin Liu, Weihuo Li, Shuti Song, Zhaofeng Yao, Yixin Jia, Sheng Yuan, Hong Yang, Nan Zhang","doi":"10.1111/jvp.13475","DOIUrl":"https://doi.org/10.1111/jvp.13475","url":null,"abstract":"<p><p>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 E<sub>max</sub> 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 AUC<sub>0-72h</sub>/MIC exhibited the most optimal fitting results (R<sup>2</sup> = .98). The MS load decreased by 1, 2, and 3 Log<sub>10</sub> 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.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971390","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}
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。
{"title":"Assessment of Single-Dose Pharmacokinetics of Oxolinic Acid in Rainbow Trout and Determination of In Vitro Antibacterial Activity Against Pathogenic Bacteria From Diseased Fish.","authors":"Richa Pathak, Sumanta Kumar Mallik, Prasanna Kumar Patil, Neetu Shahi, Krishna Kala, Raja Adil Hussain Bhat, Ranjit Kumar Nadella, Nityanand Pandey, Pramod Kumar Pandey","doi":"10.1111/jvp.13477","DOIUrl":"https://doi.org/10.1111/jvp.13477","url":null,"abstract":"<p><p>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<sup>-1</sup> 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<sup>-1</sup>) and intestine (11592.98 μg kg<sup>-1</sup>), 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<sup>-1</sup>), Lactococcus garvieae (1 μg mL<sup>-1</sup>), and Chryseobacterium aquaticum (4 μg mL<sup>-1</sup>). 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.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907003","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}
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.
{"title":"Pharmacokinetics and Alterations in Glucose and Insulin Levels After a Single Dose of Canagliflozin in Healthy Icelandic Horses.","authors":"Peter Michanek, Johan Bröjer, Inger Lilliehöök, Cathrine T Fjordbakk, Minerva Löwgren, Mikael Hedeland, Jonas Bergquist, Carl Ekstrand","doi":"10.1111/jvp.13476","DOIUrl":"https://doi.org/10.1111/jvp.13476","url":null,"abstract":"<p><p>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 T<sub>max</sub> of 7 h, a C<sub>max</sub> of 2350 ng/mL, and a t<sub>1/2Z</sub> of 28.5 h. CFZ treatment reduced glucose (AUC<sub>GLU</sub>, p = 0.001) and insulin (AUC<sub>INS</sub>, 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.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902186","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}
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。
{"title":"Pharmacokinetics and pharmacodynamics of two in-feed chlortetracycline regimens provided to beef cattle.","authors":"Alyssa R Toillion, Michael D Apley, Johann F Coetzee, Kushan Kompalage","doi":"10.1111/jvp.13474","DOIUrl":"https://doi.org/10.1111/jvp.13474","url":null,"abstract":"<p><p>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 AUC<sub>24</sub>/MIC values of 25 and 12.5 was modeled using Monte Carlo simulations. Treatment group A achieved >90% target attainment (AUC<sub>24</sub>/MIC of 25) at an MIC of 0.06 μg/mL, whereas treatment group B displayed only 12.6% target attainment (AUC<sub>24</sub>/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.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748497","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}
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":"https://doi.org/10.1111/jvp.13473","url":null,"abstract":"<p><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":null,"pages":null},"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":"https://doi.org/10.1111/jvp.13469","url":null,"abstract":"<p><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 (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 (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":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":null,"pages":null},"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":null,"pages":null},"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}