title: Should licking behavior be considered in the bioavailability evaluation of transdermal products?
abstract: Antiparasitic drugs, and especially macrocyclic lactones (MLs), are often formulated as pour-on products because of their ease of administration, convenience, and reduction of stress in treated animals. However, because of self- and allo-grooming, much of a drug administered transdermally may be systemically absorbed via the oral route, creating highly variable pharmacokinetic and pharmacodynamic response in treated (and untreated) animals. Testing bioequivalence (BE) of pour-on drugs in cattle under laboratory conditions (with restricted licking) ignores a major factor of drug disposition of these drugs and thus fails to predict therapeutic equivalence in the target population under clinical conditions of use. Therefore, the interanimal and intra-animal variability associated with licking behavior should be considered as a biological fact, rather than a noise that needs to be reduced or eliminated. As a result, it is recommended that the BE testing for pour-on products in cattle be conducted by evaluating both the mean and distribution of bioavailability parameters between the reference and test products when animals are not prevented from allo- and self-licking.
authors.affiliation: INRA, UMR1331, Toxalim, Toulouse, France. pl.toutain@envt.fr
authors.forename: P-L
authors.initials: PL
authors.lastname: Toutain
authors.forename: S
authors.initials: S
authors.lastname: Modric
authors.forename: A
authors.initials: A
authors.lastname: Bousquet-Mélou
authors.forename: J M
authors.initials: JM
authors.lastname: Sallovitz
authors.forename: C
authors.initials: C
authors.lastname: Lanusse
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000977:Antiparasitic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001522:Behavior, Animal; D001682:Biological Availability; D002417:Cattle; D005260:Female; D008297:Male; D012919:Social Behavior; D013810:Therapeutic Equivalency
chemical_list: D000977:Antiparasitic Agents