Progress on understanding the process of doramectin percutaneous absorption through ovine and bovine skin

SALLOVITZ, J.; NEJAMKIN, P.; LIFSCHITZ, A.; IMPERIALE, F.; VIRKEL, G.; LANUSSE, C.

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Congreso; XXIII International Conference of the World Association for the Advancement of Veterinary Parasitology (WAAVP); 2011

World Association for the Advancement of Veterinary Parasitology

Macrocyclic lactones are world-wide topically used to control endo and ectoparasites in cattle. A broad activity spectrum, easy administration and lack of residues in edible tissues are well established advantages for topical formulations. However, available knowledge on their pattern of transdermal absorption in ruminants is scarce. A practical in vitro method to assess dermal absorption through cattle skin was recently developed in our Lab. The objective of the work was to characterize in vitro the comparative pattern of doramectin (DRM) transdermal absorption (topical formulation) using both bovine and ovine epidermis. Hair/wool was clipped and the upper epidermal layers (500mm) split from dermis and subcutaneous tissue with a dermatome. Skin membranes (n=5) were mounted on Franz-type diffusion cells. DRM formulation (Dectomax® Pour-on for cattle, Pfizer, 0.5%) was applied on mounted skin membranes. Receptor medium was composed of buffer phosphate, bovine albumin (4.5%) and ethanol (20%) and samples collected up to 72 hours post-administration. Doramectin concentrations were determined by HPLC. DRM permeation through bovine upper epidermal layers stabilized after 38 ± 9.84 h post-administration. However, a plateau was not observed with ovine epidermal layers. Permeation fluxes were 39.92 ±10.15 (bovine) and 9.21 ±1.82 (ovine) ng·cm-2·h-1, differences being statistically significant (P<0.05). Permeation coefficients (Kp) were significantly higher (P<0.05) for bovine (1.60x10-04 ± 0.41x10-04 cm/h) compared to ovine (0.37x10-04 ± 0.07x10-04 cm/h) epidermal layers. The theoretical time required to DRM for reaching the perfusion medium (lag times) were similar between skin from both animal species (between 9.43 and 11.7 h). The differences observed in the dermal permeation in vitro kinetics may be due to quality-quantitative differences in skin composition. Ovine skin presents a higher lipid composition compare to bovine skin. This high lipid composition, along with the high DRM lipophilicity, would determine a depot effect from which DRM is slowly released. Results observed with bovine skin are in correlation with in vivo data obtained after topical treatment reported elsewhere. However, the data indicates that a limited absorption through skin may occur in sheep, which may be a serious impairment to reach an acceptable anti-parasite efficacy. Physiological species differences in skin physiology can determine marked differences in the topical absorption of highly lipophilic compounds.