“…The only common characteristics shared by these substrates are that most of these compounds are hydrophobic, positively charged or neutral compounds with a planar structure (Gottesman and Pastan, 1993;Kusuhara et al, 1998); however, negatively charged compounds, such as methotrexate and phenytoin, have also been reported as P-glycoprotein substrates Norris et al, 1996;Potschka and Loscher, 2001). P-glycoprotein is frequently detected in various resistant human tumors and often predicts poor prognosis (Chan et al, 1991;Dalton, 1994;Gregorcyk et al, 1996;Koh et al, 1992;List, 1996;Marie et al, 1991;Nooter and Sonneveld, 1994;van der Zee et al, 1995;Zochbauer et al, 1994). Thus, Pglycoprotein is believed to be one of the major mechanisms for MDR and represents a pharmacological target for reversing MDR.…”