{"title":"Study of Pharmacokinetics for Ivermectin B1a from Beagle Dogs.","authors":"Yuyang Chen, Xiaofang Huang, Zizheng Guo, Jingyu Zhang, Lixin Zhang, Renke Dai","doi":"10.1093/chromsci/bmad092","DOIUrl":null,"url":null,"abstract":"<p><p>Ivermectin has been widely used for antiparasitic drug, and has recently shown a broad-spectrum antiviral activity, including anti-Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pharmacokinetic property of ivermectin has not been fully investigated yet. During the plasma preparation, ~32-46% of ivermectin was found in the precipitation. An Liquid Chromatograph-Mass Spectrometer (LC-MS/MS) method for ivermectin in the whole blood samples from beagle dogs was developed and validated. The specificity, accuracy, precision (intra-day and inter-day), matrix effect, recovery and stability of analyte reported here are satisfied with the criteria of Food and Drug Administration (FDA)-Bioanalysis guideline. The oral administrations pharmacokinetics of ivermectin in beagle dogs under fasting and after high-fat meal were studied, and the following parameters were obtained: fasting Cmax, 104 ± 35 μg·L-1; area under the concentration-time curve (AUC0-∞), 2,555 ± 941 h·μg·L-1; and high-fat meal Cmax, 147 ± 35 μg·L-1; AUC0-∞, 4,198 ± 1,279 h·μg·L-1. When the P-gp inhibitor curcumin was also coadministrated orally, Cmax and AUC0-∞ were found to be 177 ± 57 and 4,213 ± 948 h·μg·L-1, respectively. With the comparison to fasting treatment, coadministration of P-gp inhibitor curcumin resulted in increase of the exposure of ivermectin by 1.6-fold, while the exposure after the high-fat diet versus fasting was increased approximately in 1.4-fold, indicating that alternative absorption might play an important role for increasing the exposure of ivermectin for future clinic applications.</p>","PeriodicalId":15430,"journal":{"name":"Journal of chromatographic science","volume":" ","pages":""},"PeriodicalIF":1.5000,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of chromatographic science","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1093/chromsci/bmad092","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
Ivermectin has been widely used for antiparasitic drug, and has recently shown a broad-spectrum antiviral activity, including anti-Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pharmacokinetic property of ivermectin has not been fully investigated yet. During the plasma preparation, ~32-46% of ivermectin was found in the precipitation. An Liquid Chromatograph-Mass Spectrometer (LC-MS/MS) method for ivermectin in the whole blood samples from beagle dogs was developed and validated. The specificity, accuracy, precision (intra-day and inter-day), matrix effect, recovery and stability of analyte reported here are satisfied with the criteria of Food and Drug Administration (FDA)-Bioanalysis guideline. The oral administrations pharmacokinetics of ivermectin in beagle dogs under fasting and after high-fat meal were studied, and the following parameters were obtained: fasting Cmax, 104 ± 35 μg·L-1; area under the concentration-time curve (AUC0-∞), 2,555 ± 941 h·μg·L-1; and high-fat meal Cmax, 147 ± 35 μg·L-1; AUC0-∞, 4,198 ± 1,279 h·μg·L-1. When the P-gp inhibitor curcumin was also coadministrated orally, Cmax and AUC0-∞ were found to be 177 ± 57 and 4,213 ± 948 h·μg·L-1, respectively. With the comparison to fasting treatment, coadministration of P-gp inhibitor curcumin resulted in increase of the exposure of ivermectin by 1.6-fold, while the exposure after the high-fat diet versus fasting was increased approximately in 1.4-fold, indicating that alternative absorption might play an important role for increasing the exposure of ivermectin for future clinic applications.
期刊介绍:
The Journal of Chromatographic Science is devoted to the dissemination of information concerning all methods of chromatographic analysis. The standard manuscript is a description of recent original research that covers any or all phases of a specific separation problem, principle, or method. Manuscripts which have a high degree of novelty and fundamental significance to the field of separation science are particularly encouraged. It is expected the authors will clearly state in the Introduction how their method compares in some markedly new and improved way to previous published related methods. Analytical performance characteristics of new methods including sensitivity, tested limits of detection or quantification, accuracy, precision, and specificity should be provided. Manuscripts which describe a straightforward extension of a known analytical method or an application to a previously analyzed and/or uncomplicated sample matrix will not normally be reviewed favorably. Manuscripts in which mass spectrometry is the dominant analytical method and chromatography is of marked secondary importance may be declined.