Feasibility of Using Half-Life Multipliers To Estimate Extended Withdrawal Intervals following the Extralabel Use of Drugs in Food-Producing Animals

Under the Animal Medicinal Drug Use Clarification Act of 1994, veterinarians are legally allowed to use drugs in food-producing animals in an extralabel manner. This could potentially lead to violative residues in food of animal origin. It is therefore essential that an appropriately extended withdrawal interval be established. Ideally, these extended withdrawal intervals should be calculated on the basis of the tissue half-life of the drug in the target animal. However, these data are not readily available for all drugs of extralabel use in food-producing animals. For this reason, the use of a half-life multiplier has been proposed as a simple alternative method to estimate the effective tissue half-life of a drug. Extended withdrawal intervals, estimated using various half-life multipliers, were compared with the withdrawal intervals calculated using actual tissue half-lives. For the group of drugs investigated, a half-life multiplier of 5 resulted in estimates of extended withdrawal intervals that were potentially inadequate to prevent violative tissue residues for drugs that had relatively long tissue half-lives, high tolerances, or both. This is possibly because fewer half-lives are required for these drugs to reach the target tissue concentrations following administration at label doses. Use of a smaller half-life multiplier (in this case 3) is therefore suggested to ensure that extended withdrawal intervals are adequate to prevent violative tissue residues.