The old teaching was that hydrophilic drugs may pass through the tubule and are excreted in the urine, while lipophilic drugs can cross at various places along the membrane and are reabsorbed into the plasma. Data from molecular biology techniques and gene ‘knock-out’ experiments have elucidated information concerning active transport mechanisms and have identified several novel transport proteins for organic cations and anions. There is also evidence that neutral and hydrophobic compounds are actively secreted by P-gp, an ATP-dependent membrane-bound efflux protein. Only a few major transport proteins are outlined below because a detailed discussion of the molecular biology and biochemistry of transport proteins is beyond the scope of this paper. Reviews of these data and details concerning the proposed models of transporter function may be found elsewhere. asthma inhalers
In summary, a variety of human transport proteins have been cloned, such as proteins for the transport of organic cations, including potential-sensitive, pH- and sodium-independent human organic cation transporters (OCTs) (human OCT1, human OCT2, human OCT3) and proton-organic cation exchangers (organic cation transporter novel-type [OCTN] 1, OCTN2) ; a protein for transport of neutral and cationic hydrophobic compounds, the ATP-dependent drug efflux protein (multidrug resistance [MDR] 1-type P-gp) ; proteins for the transport of organic anions including a sodium-independent organic anion transport protein (OATP) and nucleoside transporters (sodium-dependent purine nucleoside transporter (SPNT), concentrative nucleoside transporters (CNTs) 1 and CNT2 ; a prostaglandin transporter (PGT) ; and proteins for the transport of anionic conjugates, such as the ATP-dependent drug efflux transporters (multidrug resistance associated protein [MRP] 1, MRP2 or canalicular multispecific organic anion transporter [cMOAT], MRP3/cMOAT3, MRP6) often refered to as glutathione conjugate (GS-X) pumps because of their ability to transport glutathione S-conjugates.