The Pharmacokinetics and Pilot Efficacy of Levamisole Administered by Subcutaneous Injection of a Combination Product in Domestic Goats (Capra aegagrus hircus).
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
{"title":"The Pharmacokinetics and Pilot Efficacy of Levamisole Administered by Subcutaneous Injection of a Combination Product in Domestic Goats (Capra aegagrus hircus).","authors":"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","doi":"10.1111/jvp.70013","DOIUrl":null,"url":null,"abstract":"<p><p>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 (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%. 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.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.7000,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of veterinary pharmacology and therapeutics","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1111/jvp.70013","RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
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.