The Pattern of Blood-Milk Exchange for Antiparasitic Drugs in Dairy Ruminants

Abstract

The prolonged persistence of milk residual concentration of different antiparasitic drugs in lactating dairy animals should be considered before recommending their use (label or extra-label) for parasite control in dairy animals. The partition blood-to-milk ratio for different antiparasitic compounds depends on their ability to diffuse across the mammary gland epithelium. The high lipophilicity of some of the most widely used antiparasitic drugs explains their high partition into milk and the extended persistence of high residual concentrations in milk after treatment. Most of the antiparasitic drug compounds studied were shown to be stable in various milk-related industrial processes. Thus, the levels of residues detected in raw milk can be directly applicable to estimating consumer exposure and dietary intake calculations when consuming heat-processed fluid milk. However, after milk is processed to obtain milk products such as cheese, yogurt, ricotta, and butter, the residues of lipophilic antiparasitic drugs are higher than those measured in the milk used for their elaboration. This review article contributes pharmacokinetics-based information, which is useful to understand the relevance of rational drug-based parasite control in lactating dairy ruminants to avoid undesirable consequences of residual drug concentrations in milk and derived products intended for human consumption.

Keywords: antiparasitic drugs; dairy animals; plasma–milk exchange; rational use in parasite control; residues in milk dairy products.

Scheme 1

Schematic representation of the pattern of distribution (exchange) between the bloodstream and the mammary gland (milk) for hydrophilic and lipophilic drugs after treatment with different systemic routes of administration. Lipophilic compounds reach high concentrations in milk and are excreted through this route (see the text for full explanation).

Figure 1

Dose fraction recovered in milk (mean ± SEM) (n = 5). The percentages of MXD excreted in sheep´s milk after subcutaneous (SC) or oral treatment (0.2 mg/kg) are statistically different at p < 0.01 (**) from those obtained after IVM administration. The insert shows the percentages of elimination after SC or oral treatment in different species. Source: Adapted from Imperiale et al. [72].

Figure 2

Comparative profiles of moxidectin (MXD) concentration (mean ± SD) (n = 5) in plasma and milk after its pour-on administration (0.5 mg/kg) in licking-restricted (5 days) and free-licking dairy cows. Source: Adapted from Imperiale et al. [70].

Figure 3

Closantel residue levels (mean ± SD) measured in the milk collected from dairy goats (n = 6) at different times after oral treatment (10 mg/kg). (*) MRL: the maximum residue limit according to the European Medicines Agency is 45 µg/kg [102]. Source: Adapted from Iezzi et al. [106].

Figure 4

Comparative mean residual concentration of eprinomectin measured in cheese at different times of ripening (1, 20, and 40 days after elaboration) and milk collected 2 or 3 days after pour-on administration (0.5 mg/kg) in dairy sheep (a) and goats (b).The milk collected on day 2 or 3 was used to elaborate the cheeses. Source: Adapted from Imperiale et al. [82] (a) and Anastasio et al. [126] (b).