Qualyst Transporter Solutions is the world's exclusive provider of hepatic drug transporter products and contract research services utilizing the patented B-CLEAR® technology.
With over a decade of experience using our integrated in vitro hepatic model, we can support your hepatic disposition questions. No other hepatic model combines physiologic uptake and efflux transporters with hepatic metabolism. This means that our integrated model, coupled with our experience, can answer your questions about compound clearance, drug transporter interactions, cholestatic and hepatotoxic potential of your compounds.
B-CLEAR®:An In Vitro Model of In Vivo Biliary Excretion
B-CLEAR® combines in vivo-relevant uptake, metabolism, and efflux in a single, patented system that allows researchers to assess and predict biliary excretion and transporter interactions.
The B-CLEAR® model has been extensively published and utilized by academic researchers as well as regulatory and pharmaceutical scientists to answer many types of transporter questions. In addition, data from B-CLEAR® studies have been included in regulatory submissions to the FDA and EMA.
What is the B-CLEAR® Technology?
The B-CLEAR® technology refers to a patented methodology that, when applied to properly functioning hepatocytes in sandwich culture, opens the bile pockets (analogous to bile canaliculi in vivo), allowing the measurement of material that has been transported from inside the cell. Measurement of biliary efflux allows us to exclusively evaluate biliary clearance and biliary transporter interactions, as well as assess uptake, intracellular concentration, and metabolism. There are three patent platforms (including US Patent 6,780,580) that cover over 45 countries around the world.
How Do I Use The Model?
There are 3 ways researchers and customers have principally used the biliary excretion (BE) model (Figure 1):
1) Species Selection
Compare biliary clearance between rat, dog, monkey, and human
2) Phase I Clinical Support
Answer mechanistic clearance questions during clinical work
3) Drug Interaction Studies
Predict drug interactions with common co-medications
What Kind of Data Will I Obtain?
1. Species Selection
Hepatobiliary disposition of a proprietary compound evaluated in multiple species at in vivo-relevant concentrations using B-CLEAR® technology. The goal is to evaluate appropriate animal species for preclinical testing or to predict human drug clearance based on animal data.
2. Phase I Clinical Support
Compounds can be assessed for their hepatic uptake, biliary excretion, and clearance. The goal of these studies is to predict the extent of biliary excretion prior to in vivo clinical studies, to retroactively determine if bile/feces was a probable route of excretion for "missing" compound in mass balance studies.
3. Drug Interaction Studies
B-CLEAR® can be used to assess drug-transporter interactions by monitoring clinically-relevant probe substrates co-incubated with test compounds. In addition, commonly prescribed probe substrates can be used in these studies to assess potential drug interaction liabilities, thereby avoiding potentially dangerous and expensive human clinical studies. Some common probes include: digoxin (P-gp), rosuvastatin (OATPs, MRP2), nitrofurantoin (BCRP), and taurocholic acid (NTCP, BSEP).
Relevant References 1) ND Pfeifer, SL Goss, B Swift, G Ghibellini, M Ivanovic, WD Heizer, LM Gangarosa and KLR Brouwer, Effect of Ritonavir on 99mTechnetium-Mebrofenin Disposition in Humans: A Semi-PBPK Modeling and In Vitro Approach to Predict Transporter-Mediated DDIs. CPT: Pharmacometrics & Systems Pharmacology (2013)
2) Ghibellini, G., Leslie, E.M., Pollack, G.M. & Brouwer, K.L.R. Use of tc-99m mebrofenin as a clinical probe to assess altered hepatobiliary transport: integration of in vitro, pharmacokinetic modeling, and simulation studies. Pharm. Res. 25, 1851-1860 (2008).
3) Ghibellini, G., Johnson, B.M., Kowalsky, R.J., Heizer, W.D. & Brouwer, K.L.R. A novelmethod for the determination of biliary clearance in humans. AAPS J. 6, e33 (2004).
How Do I Get These Tools?
Contract research work is the easiest way to get started and engage our scientists to help solve your problems. We not only put our scientists on the job but also take advantage of our decade of history with the B-CLEAR® model and experience with hepatocytes.
We offer the three versions outlined in Figure 2 but also allow for customized study designs in order to make sure we answer the clearance question you need answered. Click here for more details.
Order our easy to use B-CLEAR® kits to do your own species or biliary clearance testing. We offer several strains for both mouse and rat, as well as dog, monkey, and human.
Each fresh kit comes with plated hepatocytes in 6- or 24-well formats, protocol, a use-license, and all of the media you need to get started. If you prefer to use cryopreserved hepatocytes, you can purchase Transporter Certified™ hepatocytes from your supplier of choice and use them for B-CLEAR® work as well as any other hepatocyte study and know they are fully functional with respect to metabolism and drug transporters.
In addition, we offer consulting time with our scientists to help you design and run your experiments, and can also help put your results into context as compared to our extensive historical database. Click here for more details.
Copyright 2011-2012 Qualyst Transporter Solutions, LLC. All Rights Reserved.B-CLEAR is a registered trademark of Qualyst Transporter Solutions, LLC.
*B-CLEAR® is covered by US Patent 6,780,580 and other worldwide patents issued & pending.