Pharmacokinetics of a topical application of moxidectin in bare-nosed wombats (Vombatus ursinus).

Sarcoptic mange is a debilitating disease that affects bare-nosed wombats (Vombatus ursinus). One of the drugs currently used for treatment is moxidectin, as it has a relatively high efficacy against endo and ectoparasites and side effects are uncommon in domestic species, thus it is considered a relatively safe drug to use at the recommended doses. Developing further understanding of the pharmacokinetics of moxidectin will aid in developing treatment regimens for sarcoptic mange in wombats. Here we analyzed the pharmacokinetic parameters of using 100 ml of moxidectin (5 g/l) applied topically. We found that mean peak plasma concentration was 0.50 ng/ml and half-life was 8 days. Moxidectin was excreted in scats with the mean peak concentration of 2461.43 ng/g (on a dry matter basis). Our study has provided the pharmacokinetic parameters of a commonly used treatment for sarcoptic mange in wombats. There were no adverse side effects recorded in the wombats after applying moxidectin topically. This study replicated real-world conditions using topical application on free-living wombats. The relatively low plasma concentration suggests the drug is not accumulating in the blood stream and is excreted via scats.

Extraction and analysis of moxidectin in wombat plasma and faeces.

Sarcoptic mange in wombats results from a skin infestation by Sarcoptes mites and if untreated, results in a slow and painful death. Moxidectin is a pesticide used to treat internal and external parasites in cattle, but has shown to effectively treat other animals, including wombats. Two methods were developed to analyse wombat plasma, and methods were also developed to analyse faeces and fur. Moxidectin-D3 was used as an internal standard and behaved almost identically to moxidectin, resulting in recoveries of 95-105 % across the three matrices, even when matrix interferences caused signal suppression as high 20 %, or when moxidectin loss was high. This was presumably due to the high binding efficiency of plasma for MOX and MOX-D3. Moxidectin limits of detection were 0.01 ng/mL in plasma, 0.3 ng/g dry weight equivalent for faeces and 0.5 ng/g for fur. This study also developed a method to isolate plasma macromolecules, allowing the extraction of bound moxidectin for quantitative purposes, with an LoQ of 0.05 ng/mL. This method was subsequently used to determine that moxidectin was 97-99.4 % bound to lipoproteins in wombat plasma and 98-99 % bound in sheep, cow and horse plasma. The method reported for plasma was quick, cheap, and conducive to large sample batches, while providing high sensitivity. While faecal samples required additional cleanup steps to reduce the matrix effect, co-extracted matrix components such as undigested chlorophyll continued to result in ionisation suppression in the MS/MS. The methods reported here were used to monitor moxidectin in wombats treated with a single pour-on treatment, and confirmed that the moxidectin concentration in wombat plasma had decreased by more than 90 % by 28 days after application, while providing protection against sarcoptic mites over the majority of their life cycle. Clearance of moxidectin occurred via faecal elimination over the four week period and while moxidectin accumulated on fur due to application as a pour-on, concentrations declined rapidly by the four week period as fur fell out and was replaced by fresh fur that did not contain moxidectin.