Moxidectin is a candidate for use as an in vivo internal standard in pharmacokinetic studies, as demonstrated with use in simultaneous tissue cage and ultrafiltration fluid collection

Abstract

In vivo ultrafiltration has been used in veterinary pharmacokinetics since the early 2000’s as an improvement on the tissue cage model which enables sampling of fluids from extra-circulatory compartments. Variability in analyte recovery from ultrafiltration samples, due to membrane fouling or tissue inflammation, has been a concern for this technique. Internal standards may be used to scale or verify the unknown result, such as is common in analytical extractions and in vivo microdialysis. Eight merino sheep were implanted with subcutaneous tissue cages and 2 weeks prior to the initiation of the study the sheep were injected with 0.2 mg/kg moxidectin subcutaneously. On the day of the study ultrafiltration probes were inserted subcutaneously. At time zero 4 mg/kg of carprofen was injected intravenously. Plasma, tissue cage, and ultrafiltration samples were taken 30 min before and 0.5, 1, 2, 3, 4, 5, 7, 24, 36, 48, 72 h after dosing. Carprofen and moxidectin concentrations were measured by LC–MS/MS. Pharmacokinetic parameters were estimated using Monolix for both the carprofen concentrations and the moxidectin corrected carprofen concentrations. The ultrafiltration probes failed to consistently produce enough sample volume to analyse. Moxidectin concentrations in the plasma and tissue cage fluid were stable throughout the 72 h sampling window. Moxidectin proved to be suitable as an in vivo internal standard for pharmacokinetic research using, tissue cages, plasma sampling and ultrafiltration probes, but the application of ultrafiltration techniques requires refinement.