Factors affecting formulation and efficacy of a sheep ectoparasiticide

Abstract

This research thesis, FACTORS AFFECTING FORMULATION AND EFFICACY OF A SHEEP ECTOPARASITICIDE used six experimental formulations containing a range of excipients and a novel ectoparasiticide, AHC-2013. The project was conducted at Yarrandoo R&D Centre, Novartis Animal Health Australasia Pty Limited (NAH), Kemps Creek, Australia. The project utilized resources and personnel approved by NAH management, e.g. animals, animal facilities, scientific analytical equipment and technical support. Three in vivo studies in sheep were conducted to investigate efficacy, drug migration in the fleece and around the body (from the site of deposition), and the scourability of an incorporated dye from the wool – each of these associated with potential production losses of meat from louse infestation or of wool from residues. The efficacy study found no formulation fully controlled the louse populations on the sheep for the 20 week period required for regulatory approval (Holdsworth et al., 2006). Despite this, several formulations displayed efficacy above 95%; these formulations, FD 0184-sol-31, FD 0184-sol-32, FD 0184-sol-33 should be the preferred formulations considered for optimization and evaluation at equivalent and higher doses. At the evaluated dose it was demonstrated that even at the application site with the highest chemical concentrations there were small residual populations of lice. Larger populations of lice were found as concentrations declined rapidly away from the application site along the backline. Mean louse counts within the control group were reduced by 31.8% 14 days after shearing, 52.2% 28 days from shearing and peaking at 52.5% on day 56 post-shearing. The decline in mean louse count started to stabilize by day 42 (51.5%) with further subtle declines up to day 56. This trend of population decline stopped at day 70 post-shearing when an increase in the mean louse population was observed. It is probable this reversal in trend was due to a resumption of the surviving parasite’s breeding cycle, and an increase in wool length and therefore the louse habitat coupled with a possible reduction and/or dilution of the overall chemical residues. Although the spray-on application method used in the evaluation of these formulations has many advantages to the end consumer it is not the only option available for application and alternatives such as higher volume spray-on and jetting solutions should also be considered in optimizing drug migration. The drug residue concentrations in wool were considerably higher on the backline close to application site (location A), as compared to the flank (locations B) and belly (location C). Although there was some variation of drug concentrations between groups for the same location and time points, there was a trend for the highest drug levels being closest to the application site and reducing significantly with distance from this area. Drug migration was found to be relatively poor with only one treatment group (FD 0184-sol-030) having drug movement over 1% (Concentration B/A*100) from location A to location B in a 42 day period. In all other groups the total concentration migration was less than 1%. Drug migration from location A to location C was less than 1% in all groups over 42 days however drug migration from location B to C varied markedly with migration of up to 63% (Concentration C/B*100; FD 0184-sol-032) down to 25% (FD 0184- sol-030). Although there was relatively good migration in concentration between the two locations, overall migration was poor given the relatively low levels of active being found at location B and C in relation to the drug concentrations found at the application area, i.e. location A. Residue depletion was slow (e.g. from days 28 to 42) so only limited conclusions can be drawn with regard to this parameter. Although a relatively slow drug residue depletion is desirable for persistent efficacy it could have potential environmental, and health and safety implications, which impact the Wool Harvesting Interval, Wool Rehandling Interval and potentially Export Slaughter Interval. Each parameter is assessed by the APVMA in the course of product registration. This low drug depletion rate should be a consideration in the design of future residue studies and particularly the timing of wool collections. Modelling of drug concentrations in wool and relative efficacy could assist in determining dose however, as seen in the efficacy and residue studies although there is a clear relationship between louse population and drug concentration in wool within treatment group and in comparison to the untreated controls. Yet the response effect was quite variable between treatment groups and would therefore be difficult to achieve without further in vivo evaluation; particularly extended residue depletion data beyond 42 days post-treatment. As drug concentration in wool data is only available for the first 42 days from treatment and the overall depletion is slow it is difficult to see an efficacy response over time to drug concentration within group. All formulations were found to be scourable to AS 4054 (Australian Standards, 2003) and therefore commercially viable. The colouring agent used was the same in all formulations. It could be assumed from the consistent scourability that the active ingredient and excipients used did not influence binding of the colouring agent to the wool fibre. This is an important consideration for commercial formulations and given this finding it would be prudent to use the same colouring agent in any future formulations.