Grace Malla, Joe Smith, Meggan Graves, Lisa Ebner, Ryan Branham, Jessica Lynch, Laura Gilliard, Julia Cutchin, Madeline Duncan, Rebecca Rahn, Michelle Buckley, Andrew Ursini, Cassandra Klostermann, Jessy Shanks, Sherry Cox
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After a 14-day washout period, the same goats were given 12 mg/kg of oral levamisole and sampled following the same time points. Levamisole concentrations were measured via liquid chromatography. A non-compartmental analysis was used to generate pharmacokinetic (PK) parameters for both formulations. After one subcutaneous (SC) injection, the maximum plasma concentration (C<sub>max</sub>), time to C<sub>max</sub> (T<sub>max</sub>), area under the curve (AUC), and elimination half-life (T<sub>1/2</sub>) were 468.57 ± 151.12 ng/mL, 2.24 ± 1.58 h, 3206.42 ± 1189.73 h ng/mL, and 2.36 ± 2.07 h, respectively. After a single oral administration, C<sub>max</sub>, T<sub>max</sub>, AUC, and T<sub>1/2</sub> were 573.21 ± 149.01 ng/mL, 0.5 ± 0.41 h, 2995.47 ± 2203.93 h ng/mL, and 3.74 ± 2.19 h, respectively. Fecal samples taken before and after subcutaneous administration had an average egg count reduction of 61.97% (p = 0.0625). The relative bioavailability of the SC injection was 185%. 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引用次数: 0
摘要
驱虫药耐药性是山羊的主要福利问题,驱虫药的有效性在于合理使用。最近,一种标记为牛用的可注射组合(左旋咪唑-多拉菌素)产品上市了。本研究的目的是比较这种新的联合药物的左旋咪唑药代动力学参数与市售的口服左旋咪唑制剂在山羊体内的作用。6只成年山羊皮下注射了9mg /kg剂量的复方制剂。在48小时内的14个时间点采集血样。在14天的洗脱期后,同样的山羊被给予12 mg/kg的左旋咪唑口服,并在相同的时间点取样。液相色谱法测定左旋咪唑浓度。采用非区室分析生成两种制剂的药代动力学(PK)参数。1次皮下注射后,最大血药浓度(Cmax)、到达Cmax时间(Tmax)、曲线下面积(AUC)和消除半衰期(T1/2)分别为468.57±151.12 ng/mL、2.24±1.58 h、3206.42±1189.73 h ng/mL和2.36±2.07 h。单次口服后,Cmax、Tmax、AUC和T1/2分别为573.21±149.01 ng/mL、0.5±0.41 h、2995.47±2203.93 h ng/mL和3.74±2.19 h。皮下给药前后的粪便样本平均卵数减少61.97% (p = 0.0625)。SC注射液的相对生物利用度为185%。考虑到生物利用度和减少卵数,可考虑将该组合产品用于寄生虫管理;然而,需要实地试验来确定其疗效和其他药效学参数。
The Pharmacokinetics and Pilot Efficacy of Levamisole Administered by Subcutaneous Injection of a Combination Product in Domestic Goats (Capra aegagrus hircus).
Anthelmintic resistance is a major welfare issue in goats, and the efficacy of anthelmintic drugs lies in judicious use. Recently, an injectable combination (levamisole-doramectin) product labeled for cattle became available. This study's goal was to compare the levamisole pharmacokinetic parameters of this new combination drug to a commercially available oral levamisole formulation in goats. Six adult goats received a 9 mg/kg dose subcutaneously of the combination product. Blood samples were collected at 14 time points over 48 h. After a 14-day washout period, the same goats were given 12 mg/kg of oral levamisole and sampled following the same time points. Levamisole concentrations were measured via liquid chromatography. A non-compartmental analysis was used to generate pharmacokinetic (PK) parameters for both formulations. After one subcutaneous (SC) injection, the maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the curve (AUC), and elimination half-life (T1/2) were 468.57 ± 151.12 ng/mL, 2.24 ± 1.58 h, 3206.42 ± 1189.73 h ng/mL, and 2.36 ± 2.07 h, respectively. After a single oral administration, Cmax, Tmax, AUC, and T1/2 were 573.21 ± 149.01 ng/mL, 0.5 ± 0.41 h, 2995.47 ± 2203.93 h ng/mL, and 3.74 ± 2.19 h, respectively. Fecal samples taken before and after subcutaneous administration had an average egg count reduction of 61.97% (p = 0.0625). The relative bioavailability of the SC injection was 185%. Considering bioavailability and egg count reduction, the combination product may be considered for parasite management; however, a field trial is needed to determine its efficacy and other pharmacodynamic parameters.
期刊介绍:
The Journal of Veterinary Pharmacology and Therapeutics (JVPT) is an international journal devoted to the publication of scientific papers in the basic and clinical aspects of veterinary pharmacology and toxicology, whether the study is in vitro, in vivo, ex vivo or in silico. The Journal is a forum for recent scientific information and developments in the discipline of veterinary pharmacology, including toxicology and therapeutics. Studies that are entirely in vitro will not be considered within the scope of JVPT unless the study has direct relevance to the use of the drug (including toxicants and feed additives) in veterinary species, or that it can be clearly demonstrated that a similar outcome would be expected in vivo. These studies should consider approved or widely used veterinary drugs and/or drugs with broad applicability to veterinary species.