Licking induced changes to the pattern of moxidectin milk elimination after topical treatment in dairy cows

Abstract

Pour-on administration of the macrocyclic lactones anti-parasitic compounds in beef and dairy cattle is now worldwide accepted. However, the information available on their milk excretion pattern, after topical administration is rather limited. Additionally, the cattle licking behaviour has been proven to affect the kinetics of these anti-parasitic compounds. The purpose of this study was to investigate the influence of the natural licking behaviour on the plasma and milk disposition of moxidectin (MXD), topically administered (500 microg/kg) in lactating dairy cows. Ten lactating Holstein dairy cows (705 kg body weight) were allocated into two experimental groups (n = 5). The licking was prevented during 5 days postadministration in animals in group I, and the remaining cows (group II) were allowed to lick freely. MXD concentrations profiles were measured in plasma and milk over 15 days posttreatment. The licking restriction period caused marked changes in MXD disposition kinetics both in plasma and milk. Both plasma and milk MXD concentrations (partial AUC 0-5 days) were significantly lower (P < 0.05) in licking-restricted cows. After the 5-day of restriction period, the animals were allowed to lick freely, which permitted the oral ingestion of MXD, situation clearly reflected both in plasma profile and milk excretion pattern. Despite the enhanced MXD milk concentrations measured in free-licking cows, drug concentrations did not reach the maximum MXD residues limit.

Should licking behavior be considered in the bioavailability evaluation of transdermal products?

“…(2005) demonstrated that the variation range for DOR plasma AUCs reached a value 1.32 in Holstein male calves. However, more recent work showed that the variation range in MOX plasma AUCs when administered as a pour‐on may reach a value of up to 7.32 in treated Holstein dairy cows (Imperiale et al. , 2009).…”

“…, 1983). The interindividual variability will contribute to the overall variability by adding to that determined by licking behavior, as illustrated in vivo by Imperiale et al. (2009) during a 5‐day licking‐restriction period.…”

“…Research by Sallovitz et al (2005) demonstrated that the variation range for DOR plasma AUCs reached a value 1.32 in Holstein male calves. However, more recent work showed that the variation range in MOX plasma AUCs when administered as a pour-on may reach a value of up to 7.32 in treated Holstein dairy cows (Imperiale et al, 2009). In licking-restricted animals (2 and 5 days of post-treatment restriction to avoid selfand allo-licking), the variation range was smaller, but the interindividual variability remained high with the variation range of 3.77 (CV = 25.6% up to 2 days post-treatment) for DOR and 2.64 (CV = 32.5% up to 5 days post-treatment) for MOX.…”

“…The interindividual variability will contribute to the overall variability by adding to that determined by licking behavior, as illustrated in vivo by Imperiale et al (2009) during a 5-day licking-restriction period. Further work on an in vitro skin absorption model useful to predict in vivo drug permeation is currently being performed by Sallovitz and coworkers in Argentina.…”

Licking behaviour induces partial anthelmintic efficacy of ivermectin pour-on formulation in untreated cattle

“…This phenomenon was better understood when it was demonstrated that the actual disposition of MLs poured on the backs of cattle was largely influenced by both self-and allo-grooming and that consequently a large fraction of the MLs was actually orally and erratically ingested by the animal itself (Laffont et al, 2001;Laffont et al, 2003) or exchanged with another animal in the herd (Bousquet-Mélou et al, 2004) rather than directly absorbed throughout the skin. The consequences of this largely overlooked "behavioural clearance" mechanism for topically administered drugs in cattle are manifold, including inconsistency of drug efficacy, unexpected residue levels (Imperiale et al, 2009), contamination of the environment (Herd et al, 1996), or the design of clinical and bioequivalence trials (Barber and Alvinerie, 2003). It is often quoted that underdosing and subtherapeutic ML exposure are factors favouring reduced anthelmintic efficacies in the field (El-Abdellati et al, 2010), which can in turn favour the emergence of anthelmintic resistance (Smith et al, 1999) for which there is experimental evidence (Van Zeveren et al, 2007).…”