Study of Pharmacokinetics for Ivermectin B1a from Beagle Dogs

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.