Not all passage across membranes is through passive absorption, there are a number of proteins involved in transporting molecules/ions into and out of cells, probably >350. Transporters probably exist in every membrane. Many were discovered after upregulation in drug-resistant tumor cells, they can have a significant impact on the pharmacokinetics of endogenous and exogenous compounds For these reasons the regulatory authorities US Food and Drug Administration (FDA) and European Medicines Agency (EMEA) request data on the effects of novel drugs on transporter protein activity. It is possible to evaluate some transporters in in vitro systems (Caco-2, LLC-PK1:MDR1) See Absorption. Transporters can have an enormous influence on the absorption, distribution or elimination of a drug. The best understood is ABCB1 also known as P-gp, MDR1 (mdr1 in rodents) this transporter is present in the blood-brain barrier, in the gut, on hepatocytes, and the kidney. It is also one of the transporters found to be up-regulated in some drug-resistant tumors.
Major Human Transporters
| Gene | Aliases | Tissue | Substrate | Inhibitor | Inducer |
| ABCB1 | P-gp, MDR1 | intestine, liver, kidney, brain, placenta, adrenal, testes | digoxin, fexofenadine, indinavir, vincristine, colchicine. topotecan, paclitaxel | ritonavir, cyclosporine, verapamil, erythromycin, ketocoanzole, itraconazole, quinidine, elacridar (GF120918) LY335979, valspodar (PSC 833) | rifampin, St John’s Wort |
| ABCB4 | MDR3 | liver | digoxin, paclitaxel, vinblastine | ||
| ABCB11 | BSEP | liver | vinblastine | ||
| ABCC1 | MRP1 | intestine, liver, kidney, brain | adefovir, indinavir | ||
| ABCC2 | MRP2, CMOAT | intestine, liver, kidney, brain | indinavir, cisplatin, | cyclosporine | |
| ABCC3 | MRP3, CMOAT2 | intestine, liver, kidney, placenta, adrenal | etoposide, methotrexate, tenoposide | ||
| ABCC4 | MRP4 | ||||
| ABCC5 | MRP5 | ||||
| ABCC6 | MRP6 | liver, kidney | cisplatin, daunorubicin | ||
| ABCG2 | BCRP | intestine, liver, breast, placenta | daunorubicin, doxorubicin, topotecan, rosuvastatin, sulfasalazine | elacridar (GF120918) | |
| SLCO1B1 | OATP1B1, OATP-C OATP2 | liver | rifampin, rosuvastatin, methotrexate, pravastatin, thyroxine | cyclosporine rifampin | |
| SLCO1B3 | OATP1B3, OATP8, | liver | digoxin, methotrexate, rifampin, | ||
| SLCO2B1 | SLC21A9, OATP-B | intestine, liver, kidney, brain | pravastatin | ||
| SLC10A1 | NTCP | liver, pancreas | rosuvastatin | ||
| SLC10A2 | ASBT | ileum, kidney, biliary tract | |||
| SLC15A1 | PEPT1 | intestine, kidney | ampicillin, amoxicillin, captopril, valacyclovir | ||
| SLC15A2 | PEPT2 | kidney | ampicillin, amoxicillin, captopril, valacyclovir | ||
| SLC22A1 | OCT-1 | liver | acyclovir, amantadine, desipramine, ganciclovir metformin | disopyramide, midazolam, phenformin, phenoxy-benzamine quinidine, quinine, ritonavir, verapamil | |
| SLC22A2 | OCT2 | kidney, brain | amantadine, cimetidine, memantine | desipramine, phenoxy-benzamine quinine | |
| SLC22A3 | OCT3 | skeletal muscle, liver, placenta, kidney, heart | cimetidine | desipramine, prazosin, phenoxy-benzamine | |
| SLC22A4 | OCTN1 | kidney, skeletal muscle, placenta, prostate, heart | quinidine, verapamil | ||
| SLC22A5 | OCTN2 | kidney, skeletal muscle, prostate, lung, pancreas, heart, small intestine, liver | quinidien, verapamil | ||
| SLC22A6 | OAT1 | kidney, brain | acyclovir, adefovir, methotrexate, zidovudine | probenecid, cefadroxil, cefamandole, cefazolin, | |
| SLC22A7 | OAT2 | liver, kidney | zidovudine | ||
| SLC22A8 | OAT3 | kidney, brain | cimetidine, methotrexate, zidovudine | probenecid, cefadroxil, cefamandole, cefazolin, |
ABC:ATP-binding cassette transporter superfamily; SLC: solute-linked carrier transporter family; SLCO: solute-linked carrier organic anion transporter family; MDR1: multi-drug resistance; MRP: multi-drug resistance related protein; BSEP:bile salt export pump; BCRP: breast cancer resistance protein; OAT: organic anion transporter; OCT: organic cation transporter; NTCP: sodium taurocholate co-transporting polypeptide; ASBT: apical sodium-dependent bile salt transporter.
In vitro models
In vitro transporter assays are usually carried out with either intact cells or isolated cell membranes over expressing the transporter of interest. The advantage of in vitro assays is that they can be performed with relatively high throughput and low costs as compared to in vivo assays. Cell lines that are mainly used for this type of assays consist of cells that polarise in vitro such as transfected MDCKII or LLC-PK cells over expressing the transporter of interest described in the Absorption section.
Transporter Classification Database
Transporter classification database
The database details a comprehensive IUBMB approved classification system for membrane transport proteins known as the Transporter Classification (TC) system. The TC system is analogous to the Enzyme Commission (EC) system for classification of enzymes, except that it incorporates both functional and phylogenetic information. Curated annotations, TC numbers, and external references for 2151 families of transport proteins are provided. Transport systems are classified on the basis of five criteria, and each of these criteria corresponds to one of the five numbers or letters within the TC accession for a particular type of transporter.
The database includes structural information, disease relevance and over 26,000 references.
ABCB1 in more detail