Regulatory Guidance
➦ PortaCellTec – the pathfinder for your drug
Transporters are membrane proteins whose primary function is to facilitate the flux of molecules, like nutrients or endogenous substrates (e.g. sugar, amino acids, nucleotides) into and out of cells.
However, the specificity of these transporters is not strictly restricted to these physiological substrates. Drugs that bear significantly structural similarity to the physiological substrates have the potential to be recognized and transported by these transporters.
Consequently, these transporters play key roles in determining the bioavailability, therapeutic efficacy, and pharmacokinetics of a variety of drugs.
According to US Food and Drug Administration (FDA), European Medicines Agency (EMA) Japanese Pharmaceuticals and Medical Devices Agency (PMDA) guidelines (see below) PortaCellTec provides transporter assays, to proof the interaction of drugs and their metabolites with selected cellular transporter proteins, which facilitate the flux of molecules into cells (SLC transporters) and out of the cells (ABC transporters).
➦ Guidance for Industry
‣ US Food and Drug Administration (FDA)
- FDA – In Vitro Metabolism- and Transporter- Mediated Drug-Drug Interaction Studies
- FDA – Guidance for Industry – Draft Guidance (2017)
- FDA – Drug Interaction Studies − Study Design, Data Analysis, and Implications for Dosing and Labeling Recommendations (2012)
- FDA – Major human transporters (2006)
- FDA – Drug Interaction Studies − Study Design, Data Analysis, and Implications for Dosing and Labeling – Draft Guidance For Industry (2006)
‣ European Medicines Agency (EMA)
- EMA – Guideline on the Investigation of Drug Interaction (2012)
- EMA – Guideline on the Investigation of Drug Interaction – Draft Guidance (2010)
‣ Japanese Pharmaceuticals and Medical Devices Agency (PMDA)
- Japan – Guideline on the Investigation of Drug Interactions (2014)
‣ The International Transporter Consortium (ITC)
- The International Transporter Consortium – Membrane transporters in drug development: the full report from the International Transporter Consortium, March 2010, is available from Nature Reviews
➦ More Information:
- A public drug transporter database ➔ UCSF-FDA TransPortal
- SLC (Solute Carrier) transporter database ➔ Bioparadigms
| Transporter | Gene | Drug Elimination | ITC/FDA | EMA | PMDA |
|---|---|---|---|---|---|
| OAT1 ▸ | SLC22A6 | renal | + | + | + |
| OAT3 ▸ | SLC22A8 | renal | + | + | + |
| OATP1B1 ▸ | SLCO1B1 | hepatic | + | + | + |
| OATP1B3 ▸ | SLCO1B3 | hepatic | + | + | + |
| OCT1 ▸ | SLC22A1 | hepatic | propose | + | – |
| OCT2 ▸ | SLC22A2 | renal | + | + | + |
| MATE1 ▸ | SLC47A1 | hepatic/renal | + | consider | + |
| MATE2K ▸ | SLC47A2 | renal | + | consider | + |
| MDR1 ▸ | ABCB1 | hepatic/renal | + | + | + |
| BCRP ▸ | ABCG2 | hepatic | + | + | + |
| BSEP ▸ | ABCB11 | hepatic | prefer | consider | – |
