Pharmacokinetic studies of ivermectin: effects of formulation.

Studies are reported which describe the effects of formulation, animal species, and route of administration on the pharmacokinetics of ivermectin. Biological half-life t1/2 increases in the order: swine (0.5 day) less than dogs (1.8 day) less than cattle approximately equal to sheep (2.8 day). Formulation modifications, based upon the solubility properties of the drug, have been directed towards the development of a nonaqueous injectable formulation for cattle and an aqueous vehicle for horses. Bioavailability following subcutaneous injection in cattle can be regulated by control of injection solvent composition: a vehicle composed of a mixed aqueous-organic solvent exhibits pharmacokinetic properties (i.e., Cp, t1/2, AUC, and F) intermediate between those furnished by an aqueous formulation and via a purely nonaqueous solvent. The longer apparent biological half-life from this latter vehicle (t1/2 = 8.3 days) confirms that a slow absorption process dominates the pharmacokinetics in the nonaqueous injectable product to produce an effective controlled-release formulation. These bioavailability results illustrate the increase in the concentration of an organic solvent and a concomitant decrease in surfactant concentration in a micellar aqueous system for prolonged drug delivery via injection.