Mashayekhi S O, Sattari M R, Routledge P A
National Public Health Management Research Center, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, I.R.Iran.
Res Pharm Sci. 2010 Jul;5(2):99-106.
Several transporters appear to be important in transporting various drugs. Many patients, who receive morphine as analgesic medication, also receive other medications with potency of changing morphine transport by affecting P-glycoprotein (P-GP) and oatp2 transport system. This could influence morphine pharmacokinetics and pharmacodynamics. The aim of present study was to elucidate the transport mechanisms involved in transporting morphine via MDCKII and MDCK-PGP cells. Morphine permeability was examined in the presence of various compounds with ability in inhibiting different transport systems including: digoxin, probenecid and d- glucose. The effect of morphine concentration changes on its transport was also examined. Morphine concentration was measured using HPLC with electrochemical detector. Morphine permeability via a MDCK II cells was greater than sucrose permeability, and reduced when a P-GP expressed cell line was used. Its permeability was increased significantly in the presence of a strong P-GP inhibitor. Morphine permeability decreased significantly in the presence of digoxin but not in the presence of d-glucose or probenecid. These results showed that morphine was a P-GP substrate, and digoxin related transporters such as oatp2 were involved in its transport. Morphine was not substrate for glucose or probenecid-sensitive transporters.
几种转运体在多种药物的转运过程中似乎起着重要作用。许多接受吗啡作为镇痛药物治疗的患者，同时还会接受其他药物治疗，这些药物有可能通过影响P-糖蛋白（P-GP）和有机阴离子转运多肽2（oatp2）转运系统来改变吗啡的转运。这可能会影响吗啡的药代动力学和药效学。本研究的目的是阐明通过MDCKII细胞和MDCK-PGP细胞转运吗啡的机制。在存在多种能够抑制不同转运系统的化合物（包括地高辛、丙磺舒和d-葡萄糖）的情况下，检测吗啡的通透性。同时也检测了吗啡浓度变化对其转运的影响。使用带有电化学检测器的高效液相色谱法（HPLC）测定吗啡浓度。通过MDCK II细胞的吗啡通透性大于蔗糖通透性，而当使用表达P-GP的细胞系时，吗啡通透性降低。在存在强效P-GP抑制剂的情况下，其通透性显著增加。在存在地高辛的情况下，吗啡通透性显著降低，但在存在d-葡萄糖或丙磺舒的情况下则没有降低。这些结果表明，吗啡是P-GP的底物，并且地高辛相关的转运体如oatp2参与了其转运过程。吗啡不是葡萄糖或丙磺舒敏感转运体的底物。
