FDA-compliant Transporter Studies at Solvo Biotechnology

February 24th 2009:

SOLVO Biotechnology

• provides all the definitive in-vitro P-gp assays that comply with the 2006 FDA Draft Guidance on assessing drug-drug interactions
• has the widest range of transporter assay systems that satisfies all the upcoming FDA requirements for efflux and uptake transporters
• has unparalleled knowledge on transporters, and has the biggest drug transporter R&Ð department publishing regularly in peer-reviewed journals
• was the first CRO to recognize the importance of studying various drug transporters individually
• continuously expands its portfolio based on the latest results in transporter science, the needs of the pharmaceutical industry and the various regulatory agencies such as FDA and EMEA

Why is P-gp important?

• P-gp drug efflux transporter is present in all pharmacological barriers influencing the ADMETox properties of drugs
• drugs that are substrates or inhibitors of P-gp may participate in drug-drug or drug-nutrient interactions, leading to modified bioavailability of the drug and to serious side effects such as morbidity in case of drugs with narrow therapeutic index

What are the main characteristics of SOLVO's FDA-compliant P-gp PREDISCREEN^TM services?

• studies can be conducted using human Caco-2, or MDR1-MDCKII cell lines according to your request
• the general protocol applies two P-gp inhibitors in the Caco-2 assay recommended by the FDA: Verapamil and Ketoconazole
• it can identify P-gp substrate and inhibitory properties of your NCE, IND or NDA
• it can provide IC₅₀ data for the inhibition of digoxin transport
• it is a flexible design for optimal cost and quick turn-around time
• a clear and consistent flow-chart with decision points describes SOLVO's FDA-compliant P-gp studies

SOLVO Biotechnology is the right choice for P-gp-related studies!

• SOLVO has the most comprehensive P-gp technology platform from HT in-vitro assays to in-vivo studies
  • in-vitro assays
    • P-gp PREDIVEZ^TM Kit: this vesicular transport assay is a unique HT SOLVO technology that identifies all the compounds that interact with P-gp
    • P-gp PREDEASY^TM Kit: SOLVO's HT ATPase assay is able to distinguish substrates and inhibitors
    • P-gp Calcein assay: SOLVO's proprietary cellular dye efflux assay
    • Caco-2 monolayer assays are available at different levels of complexity: basic, custom and FDA setup. Transporter specific interactions can also be investigated with the use of P-gp and BCRP substrates and inhibitors
    • MDR1-MDCKII monolayer assays
  • in-vivo services
    • rat brain microdialysis uses quinidine as reporter substrate, and PSC833 as a specific P-gp inhibitor
• SOLVO suggest tailor-made solutions to optimize study design and the right combination of the appropriate assays
• you can save money and time by choosing the most appropriate SOLVO P-gp assays for the different stages of your drug development

Which additional drug transporters are under FDA consideration?

• Efflux transporters: BCRP, BSEP
• Uptake transporters: OATP1B1, OATP2B1, OATP1B3, NTCP, OCT2, OAT1, OAT3

Products and PREDISCREEN^TM service solutions for these transporters:

• BCRP: BCRP-MDCKII monolayer assay, Caco-2 monolayer assay with BCRP inhibitor, BCRP-PREDEASY^TM Kit, BCRP-PREDIVEZ^TM Kit, BCRP cellular dye efflux assay (Hoechst 33342), double-transfectant OATP2B1/BCRP-MDCKII monolayer assay, rat liver perfusion, rat brain microdialysis
• stably transfected uptake transporter cell lines: OATP1B1, OATP2B1, OATP1B3, NTCP, OCT2, OAT1, OAT3
• BSEP: vesicular transport assay
• OATP1B1: cellular assay
• OATP2B1: cellular assay
• OATP1B3: cellular assay
• NTCP: cellular assay
• OCT2: cellular assay
• OAT1: cellular assay
• OAT3: cellular assay

For additional information please contact SOLVO at FDAcompliance@solvo.com or follow the following links:

1. SOLVO Product and PrediScreen service catalogue
2. Utilization of SOLVO products and services in the drug development pipeline
3. SOLVO membrane transporter solutions according to the Biopharmaceutics Drug Disposition Classification System (BDDCS)