The relative plasma availabilities of ivermectin in reindeer (Rangifer tarandus tarandus) following subcutaneous and two different oral formulation applications

Abstract

Background: Overwintering (breeding) reindeer (Rangifer tarandus tarandus) are commonly treated with ivermectin against parasitic infestations once yearly in autumn-winter roundups. The only preparations registered to reindeer are those for subcutaneous injection. However, also oral extra-label ivermectin administration is used. Twenty-six, 8-month-old reindeer calves were randomly allocated into three groups. Group 1 (n = 9) received oral ivermectin mixture (Ivomec® vet mixt. 0.8 mg/ml, oral ovine liquid drench formulation), Group 2 (n = 9) oral ivermectin paste (Ivomec® vet 18.7 mg/g equine paste), and Group 3 (n = 8) subcutaneous injection of ivermectin (Ivomec® 10 mg/ml vet inj.), each group at a dose of 200 μg/kg body weight. Blood samples were collected at treatment and at days 1, 2, 3, 6, 9 and 16 post treatment. Plasma concentrations of ivermectin were determined by high-pressure liquid chromatography (HPLC) with fluorescence detection.

Results: The peak plasma concentration (Cmax) was reached by 2 days after each treatment. The Cmax and Area Under Curve (AUC) differed significantly between the groups: Cmax was 30.2 ± 3.9, 14.9 ± 5.7 and 63.1 ± 13.1 ng/ml, and AUC∞ was 2881 ± 462, 1299 ± 342 and 6718 ± 1620 ng*h/ml for groups 1, 2 and 3, respectively (mean ± standard deviation).

Conclusions: The differences in plasma concentrations of ivermectin are concomitant with earlier observed differences in antiparasitic efficacy, which discounts the use of the equine paste in reindeer in favour of the oral ovine liquid drench formulation, or preferably, the reindeer-registered subcutaneous injection formulation.

Figure 1

An example HPLC chromatogram for an actual plasma sample from a reindeer treated with ivermectin by oral administration of equine paste (Group 2) at the dose of 200 μg/kg. Sample from day 2 post treatment, concentration determined to 9 ng/ml. HPLC detector attenuation: 3. Each plasma sample for analysis (1.0 ml) was supplemented with 10 ng abamectin (internal standard) before extraction and sample preparation. The plasma concentration calculation was based on the HPLC software-generated heights of the ivermectin B1a and abamectin Bla peaks using the equation given above.

Figure 2

Mean ( + standard deviation) plasma ivermectin concentration (ng/ml) in three groups of reindeer treated with ivermectin (x-axis: days after treatment), 1) broken line, Ivomec ® vet mixt. 0.8 mg/ml orally n = 9; 2) dotted line, Ivomec ® vet 18.7 mg/g paste orally n = 9 ; 3) solid line, Ivomec ® 10 mg/ml vet inj. subcutaneously n = 8 . All treatments at a dose of 200 μg/kg.