PIII‐76

BACKGROUND While several drugs are commercially available as the pamoate salts, information on the systemic exposure of pamoic acid (PA) from such drug products is not available in the literature. This study was conducted to determine the pharmacokinetics of PA from a marketed formulation, hydroxyzine pamoate. METHODS The study was conducted as open‐label in 6 healthy Caucasian male subjects (25 to 37 years). Each subject received 100 mg hydroxyzine pamoate once on Day 1 and every 6 hours from Days 2 to 4 (9 oral doses). Blood samples were obtained on Days 1 and 4 at 0, 1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hr after the dose. PA concentrations were measured using a validated HPLC method with fluorescence detection and analyzed using non‐compartmental method. RESULTS Plasma concentration‐time profile of PA showed biphasic elimination. PA was rapidly absorbed with time to maximal concentration of 3 hr on Day 1 and 3.5 hr on Day 4. Mean apparent half‐life on Days 1 and 4 were 5.7 and 7.0 hr, respectively. Upon multiple dosing, oral clearance ranged from 12 to 115 L/hr and oral volume of distribution ranged from 99 to 1200 L. Maximum average steady state concentrations of PA were 715 ng/mL. CONCLUSIONS PA is rapidly absorbed and eliminated from the systemic circulation on oral administration of hydroxyzine pamoate. The concentrations of PA reported in this study provide information on the systemic exposure of PA. Further studies are warranted to evaluate the pharmacokinetics of PA from other pamoate salts. Clinical Pharmacology & Therapeutics (2005) 79 , P79–P79; doi: 10.1016/j.clpt.2005.12.284