CARBIDOPA/LEVODOPA, SELEGILINE DO NOT EFFECT THE CLEARANCE OF PRAMIPEXOLE. AMANTADINE MAY SLIGHTLY DECREASE THE CLEARANCE. CIMETIDINE, A KNOWN INHIBITOR OF RENAL TUBULAR SECRETION OF ORGANIC BASES VIA THE CATIONIC TRANSPORT SYSTEM, CAUSED A 50% INCREASE IN PRAMIPEXOLE AUC AND A 40% INCREASE IN HALF-LIFE. RANITIDINE, DILTIAZEM, TRIAMTERENE, VERAPAMIL, QUINIDINE, AND QUININE DECREASES THE ORAL CLEARANCE OF PRAMIPEXOLE BY ABOUT 20%, WHILE THOSE SECRETED BY THE ANIONIC TRANSPORT SYSTEM (E.G., CEPHALOSPORINS, PENICILLINS, INDOMETHACIN, HYDROCHLOROTHIAZIDE, AND CHLORPROPAMIDE) ARE LIKELY TO HAVE LITTLE EFFECT ON THE ORAL CLEARANCE OF PRAMIPEXOLE. SINCE PRAMIPEXOLE IS A DOPAMINE AGONIST, IT IS POSSIBLE THAT DOPAMINE ANTAGONISTS, SUCH AS THE NEUROLEPTICS (PHENOTHIAZINES, BUTYROPHENONES, THIOXANTHENES) OR METOCLOPRAMIDE, MAY DIMINISH THE EFFECTIVENESS OF PRAMIPEX.