Comparative depletion of ivermectin and moxidectin milk residues in dairy sheep after oral and subcutaneous administration

Abstract

Ivermectin (IVM) and moxidectin (MXD) are broad-spectrum endectocides belonging to the avermectin/milbemycin class of antiparasitic drugs not approved for use in dairy sheep. However, these compounds are widely used extra-label to control endo-and ecto-parasites in lactating dairy sheep. Effects of the route of administration on the pattern of IVM and MXD excretion in milk were comparatively characterized in lactating dairy sheep. The relationship between the milk and plasma disposition kinetics after subcutaneous (s.c.) and oral administration at 200 mg/kg body weight was also evaluated. IVM and MXD concentration profiles were measured in milk and plasma using a specific HPLC-based methodology. IVM and MXD were extensively distributed from the bloodstream to the mammary gland and large quantities, particularly for MXD, were excreted in milk. Residual concentrations of IVM were recovered in milk up to 11 d (oral treatment) or 25 d (s.c. treatment) post treatment. However, high MXD concentrations were detected in milk between 1 h and 35 d after its oral and subcutaneous administration. MXD concentrations as high as 3 . 77 ng/ml (oral) and 30 . 3 ng/ml (s.c.) were measured in milk at day 35 post administration. A higher MXD excretion in milk, compared with that of IVM, was obtained for both administration routes. An extensive plasma to milk distribution pattern was observed, being the area under the concentration-time curve of MXD obtained in milk up to 14-fold higher than that measured in the bloodstream. The total fraction of the administered dose excreted in milk for MXD was significantly higher than that for IVM, which agrees with the well known higher MXD lipophilicity. The long persistence of milk residual concentrations of MXD and IVM in lactating dairy sheep should be seriously considered before their extra-label use is recommended.

Relative bioavailability and comparative clinical efficacy of different ivermectin oral formulations in lambs

“…which have shown to affect the pharmacokinetic behaviour of IVM [13]. On the other hand and as it was previously reported, IVM plasma concentrations is higher after the SC compared to the IR administration [16,17]. Although similar concentration profiles were measured in the abomasal mucosa after treatment by both routes, markedly lower IVM concentrations were recovered in the abomasal contents after its SC injection.…”

Excretion of Moxidectin into Breast Milk and Pharmacokinetics in Healthy Lactating Women

“…A study in lactating dairy sheep showed that after administration of a single oral dose of 200 g/kg of body weight of moxidectin, 2.1% Ϯ 0.33% of the administered dose was excreted in milk for more than 35 days after dosing (7). The ratio of the total AUC curve for moxidectin in breast milk (AUC milk ) to the AUC was 14.3 Ϯ 1.88, indicating that although the total amount of drug that entered the breast milk was small, moxidectin preferentially entered breast milk compared to results for plasma.…”

Moxidectin and ivermectin metabolic stability in sheep ruminal and abomasal contents

“…, 1997). A markedly longer residence time for MXD compared with IVM, has also been observed after oral treatment in sheep (Imperiale et al. , 2004; Molento et al.…”

“…The oral administration of the ML in sheep has been shown to result in lower systemic availability of the parent compounds compared with the subcutaneous treatment (Marriner et al. , 1987; Imperiale et al. , 2004; Lespine et al.…”