PI‐74

AIMS Itopride, a new prokinetic drug, is highly bound to plasma proteins. This study aimed at assessing the influence of itopride on the protein binding of two drugs with narrow therapeutic indices: digoxin and warfarin. METHODS In vitro protein binding in human plasma was determined using an equilibrium dialysis method after incubation at 37°C for 3 hours for warfarin and 6 hours for digoxin. Drugs were assayed in plasma and phosphate buffer by LC/MS/MS. Itopride and digoxin were tested at concentrations close to low, middle, and high therapeutic range, namely: 100 ng/mL, 250 ng/mL and 500 ng/mL for itopride and 0.8 ng/mL, 1.7 ng/mL and 2.5 ng/mL for digoxin. Warfarin was tested at concentration close to low and high therapeutic range, 1.8 μg/mL and 2.6 μg/mL. Each value is the mean of three assays. RESULTS Mean (S.D.) % of free digoxin or warfarin in human plasma at equilibrium (See Table)Itopride (ng/ mL) Digoxin (0.8 ng/ mL) Digoxin (1.7 ng/ mL) Digoxin (2.5 ng/ mL) Warfarin (1.8 μg/ mL) Warfarin (2.6 μg/ mL)0 99.3 (23.4) 71.4 (9.1) 81.5 (32.8) 1.4 (0.4) 1.7 (0.8) 100 120.0 (22.4) 92.8 (1.3) 79.2 (3.5) 2.6 (1.0) 2.4 (1.2) 250 107.5 (41.7) 80.0 (8.2) 90.7 (13.6) 2.0 (1.0) 1.7 (0.8) 500 78.3 (12.2) 90.0 (14.0) 73.4 (14.8) 1.9 (0.7) 1.7 (0.8)CONCLUSIONS These data suggest that itopride is not at risk of producing a clinically significant drug‐drug interaction with digoxin. The clinical relevance of the increase seen with warfarin at itopride concentration of 100 ng/mL remains to be clarified. Clinical Pharmacology & Therapeutics (2005) 79 , P26–P26; doi: 10.1016/j.clpt.2005.12.095