Clinical Pharmacology of Alcaftadine, a Novel Antihistamine for the Prevention of Allergic Conjunctivitis

Abstract Purpose: In this report, we characterize the in vitro pharmacokinetic properties of a new antihistamine, alcaftadine. In addition, we report results from phase 1 studies of several ophthalmic formulations of alcaftadine and examine the pharmacokinetic properties of one formulation in detail. Methods: In vitro pharmacology employed a human liver microsome assay combined with index substrates or inhibitors for specific cytochromes. Metabolic fate of 14C-alcaftadine was determined by high-performance liquid chromatography–based separation of parent compound from metabolites. Plasma protein binding was determined by equilibrium dialysis using 3H-labeled alcaftadine and 3H-labeled alcaftadine carboxylic acid metabolite. Relative tolerability (comfort) of 4 concentrations and 3 formulations of alcaftadine ophthalmic solution was assessed in 2 double-masked, randomized, placebo-controlled, contralateral studies in which formulations were compared to Tears Naturale II (placebo) in normal adult subjects. ...