Wednesday, February 23, 2005

12:00 PM – 1:00 PM – REGISTRATION

 

12:00 PM – 5:00 PM - EXHIBITS

 

12:50 PM - 1:00 PM - Exhibitor Presentation - Tissue Transformation Technologies, Inc.

 

1:00 PM – 1:45 PM  **NEW START TIME**

Basis of Membrane Transport Process (Ikumi Tamai, Tokyo University of Science; Chiba, JAPAN) Membrane transport process for drugs is not simple because multiple pathways may be involved for single drug compound, including passive diffusion and carrier-mediated transport mechanisms.  Carrier-mediated process includes influx and efflux transporters and the resultant membrane transport process will be more complicated.   Many factors such as membrane potential, pH, and ion species affect the transporter activity as well as passive diffusion.  As the introduction of this conference, the definition and characteristics of membrane transport of drugs via transporters are described.

 

1:45 PM - 2:30 PM

An Update of SLC Transporters (Hiroyuki Kusuhara, University of Tokyo; Tokyo, JAPAN) Transporters for facilitated diffusion and secondary active transporters are classified as solute carrier (SLC) by HUGO.  SLC is now divided into more than 40 groups and each of them consisted of several members.  SLC includes pharmacokinetically important transporters such as OATP, OCT, OAT, and PEP.  SLC also includes physiologically important transporters for nutrients, neurotransmitters, and others and could be used as pharmacological targets for drug discovery.    The classifications and characteristics of SLC transporters mainly involved in drug transport are described.

 

2:30 PM – 2:45 PM - BREAK

 

2:45 PM - 3:30 PM

ABC Transporters in Boundaries of Body Compartments (Bruno Stieger, University Hospital, Zurich, SWITZERLAND) ABC proteins are primary active transporters containing an ATP-binding cassette. Many are located in boundaries between body compartments, such as epithelia or blood brain barrier. They utilize ATP and establish concentration gradients of endogenous and exogenous compounds. Their importance in physiology is highlighted by the fact that 12 out of 48 ABC genes are linked to human diseases. ABC-transporters accept drugs or their metabolites as substrates, thereby significantly contributing to intestinal drug absorption or metabolite excretion in liver or kidney.

 

3:30 PM - 4:15 PM

In vitro Methods for Transport Studies (Yuichi Sugiyama, University of Tokyo; Tokyo, JAPAN) Transporters will be available for the delivery of drugs to targeting tissue, development of drugs with ideal pharmacokinetic property, and examining an effect of genetic polymorphisms and drug-drug interaction.  In order to obtain an insight into the membrane transport process, in vitro methods have been developed which include membrane vesicles, and isolated and cultured cells from the liver.  In addition, molecular cloning of transporters has enabled us to apply their expression systems in mammalian cells to drug development.  In addition, vectorial transport, achieved by a coordination of uptake and efflux transporters, has been established in a polarized cell line, which can be applied for evaluation of hepatobiliary and urinary transport.  The presentation includes these methods, and how we can evaluate the contribution of transporters involved.

 

4:15 PM - 4:30 PM – BREAK

 

4:30 PM - 5:15 PM

Methods for estimation of drug transport:   transfection systems, intact cells, and whole organs or whole body (Sandy Pang, University of Toronto, Toronto, ONT, CANADA) It is being increasingly recognized that transporters play an important role in drug disposition.  Several methods exist for the study of transporters.  These include: expression systems, membrane vesicles (driving force, ions), intact cells, perfused organs and dilution profiles involving markers such as albumin, sucrose and water, and intact animals exemplified by gene knockout mice (KO) or mutant animals. However, assessment of the impact of transporters in vivo requires integration of transporter function for influx and efflux in addition to intracellular metabolism and excretion not only within the organ but also in other organs. The presence of other transporters/enzymes or compensatory mechanisms also need to be considered.

 

5:15 PM – 6:00 PM - Discussion    

 

END OF DAY 

Thursday, February, 24, 2005

 

8:00 AM – 9:00 AM – REGISTRATION

 

8:00 AM – 5:00 PM – EXHIBITS

 

9:00 AM – 9:45 AM

Intestinal Transporters: Mechanisms and Involvement in Drug Absorption (Ikumi Tamai, Tokyo University of Science; Chiba, JAPAN) Since nutrient transporters very efficiently absorb physiological compounds; they should be promising as the tools for the improvement of drug absorption.   Intestinal transporters such as PEPT1, OATP and other unidentified ones facilitate drug absorption, while efflux transporters such as P-glycoprotein sometime work as drug absorption barriers.  Examples of drug absorption by transporters, practical application of influx transporters for the improvement of drug absorption, and the significance and the limitation of the effect of efflux transporters in drug absorption are described. 

 

9:45 AM – 10:30 AM

Hepatic Transporters: Factors Affecting Systemic Bioavailability and Biliary Excretion (Yuichi Sugiyama, University of Tokyo; Tokyo, JAPAN) One of the important factors in governing the systemic bioavailability and hepatic clearance of drugs is the biliary excretion and/or metabolism following its hepatic uptake. Organic anion transporting polypeptides (OATPs) and organic cation transporter 1 (OCT1) have been shown to account for the hepatic uptake of organic anions and cations, respectively, while MRP2, BCRP and MDR1 are involved in the excretion of their substrates from cells to the bile. We have established double-transfected MDCK II cells where one of the uptake transporters (OATP2/OATP-C and OATP8) is expressed on the basolateral membrane and one of the efflux transporters (MRP2, MDR1 and BCRP) is simultaneously expressed on the apical membrane as an in vitro model for hepatobiliary transport.  Such a double transfected cell system may be used to assess the hepatobiliary clearance of drugs and the transporter mediated drug-drug interactions.

 

10:30 AM - 10:45 AM – BREAK

 

10:45 AM – 11:30 AM

Evaluation of the Removal of Drugs by the First-pass Effect in Intestine and Liver  (Sandy Pang, University of Toronto, Toronto, ONT, CANADA) The intestine and liver are an important tissue-organ pair that regulates drug absorption and first-pass removal during oral administration.  The intestine is an absorptive tissue that also expresses efflux transporters at the apical membrane as well as metabolic enzymes within enterocytes.  Modeling of transporters and metabolism within the intestinal tissue is complex since the absorbed drug may be effluxed out.  Moreover, drugs in the intestinal lumen are subject to greater extents of intestinal metabolism or secretion than drugs in the systemic circulation. Drugs leaving the intestine reach the liver, the next organ in that is arranged in sequence.  The liver is the most important drug metabolizing organ that is endowed with phase I and II enzymes and transporters for sinusoidal entry and biliary excretion. The transporters and enzymes are heterogeneously distributed within segments of the small intestine and the three zonal regions, 1, 2, and 3 (or periportal, midzonal, and perivenous).  Intestine/liver models exist to describe the interactions between intestinal and hepatic transporters and enzymes in the first-pass effect.

 

11:30 AM – 12:15 PM

Renal Transporters Involved in the Urinary Excretion of Drugs (Hiroyuki Kusuhara, University of Tokyo; Tokyo, JAPAN) The tubular secretion occurs at the proximal tubules in the kidney where transporters are involved, and it has been characterized by organic anion and cation transport systems.  Recent progress has revealed the molecular characteristics of transporters involved in the uptake process of organic anions and cations.  They show broad substrate specificity.  The presentation will include the molecular characteristics of these transporters, and the method of evaluating contribution of transporters at the basolateral membrane.  Recent findings regarding the apical efflux mechanisms will be included.

 

12:15 PM – 1:30 PM - LUNCH

 

1:30 PM - 2:15 PM

Molecular Characteristics of Efflux Transporters at the Blood-brain Barrier (Hiroyuki Kusuhara, University of Tokyo; Tokyo, JAPAN) The blood-brain barrier (BBB) prevents the uptake of drugs by highly developed tight junctions which connects endothelial cells and minimize the paracellular transport, and active efflux mechanisms.  P-glycoprotein plays a dispensable role as detoxification mechanisms at the BBB.  In addition, in vivo studies in rats have demonstrated an involvement of multispecific organic anion transporters in the efflux transport from the brain.  The presentation will introduce these organic anion transporters, and also recently identified ABC transporters such as BCRP and MRP4.  Multispecific transporters have been shown to mediate the uptake at the luminal membrane which may be available for the delivery of drugs to the brain.  The presentation will refer to these transporters as well.

 

2:15 PM – 3:00 PM

Mechanisms of Transporter Gene Expression and their Effects on Membrane Transport Activity and Drug Pharmacokinetics (Jyrki J. Eloranta, Laboratory of Molecular Gastroenterology and Hepatology, University Hospital Zurich, SWITZERLAND) The intestinal absorption and the hepatic clearance of drugs is mediated by numerous drug transporter proteins expressed at the plasma membrane of hepatocytes and enterocytes. The expression level of these transporters determines drug bioavailability and pharmacokinetics. For most transporters, the regulatory mechanisms that control expression occur primarily at the level of gene transcription. Transporter genes are regulated by various nuclear receptors and their respective ligands, which may influence drug efficacy, the onset of drug-drug interactions and the choice of drug.

 

3:00 PM – 3:15 PM – BREAK

 

3:15 PM – 4:00 PM

In Vivo Consequence of Transporters and Approaches to Predict Inter-individual Variation and Drug Interaction (Yuichi Sugiyama, University of Tokyo; Tokyo, JAPAN) The use of transporter function offers the possibility of delivering a drug to the target organ, avoiding distribution to other organs (thereby reducing the chance of toxic side-effects), controlling the elimination process, and/or improving oral bioavailability. It is useful to select appropriate medicine in therapy that may or may not interact with transporters, depending on whether such an interaction is desirable. The changes in pharmacokinetics due to genetic polymorphisms and drug-drug interactions involving transporters can often have a direct and adverse effect on the therapeutic safety and efficacy of many therapeutically important drugs. I will share with you our most recent data on the transporter-mediated drug-drug interactions and genetic polymorphism of organic anion transporter (OATP2/OATP-C) and other transporters taking clinically important drugs as examples.

 

4:00 PM – 4:45 PM

Pharmacogenetics and SNPs of Transporters (Ikumi Tamai, Tokyo University of Science; Chiba, JAPAN) Information of SNPs in drug transporters is growing, including OATP, OCT, MDR1, BCRP and others.  Some of SNPs affect the apparent activity, while others do not.  The evaluation of the SNPs on the apparent activity is not easy.  Since SNPs may change the expression level, intracellular membrane sorting, and affinity/functionality of the transporter proteins, the effect of SNPs is sometimes affected by the method used for the analysis.   The present status of the important SNPs in drug transporters is described.

 

4:45 PM – 5:30 PM

Effect of Transporters on Intestinal and Hepatic First-pass Metabolism (Jiunn Lin, Merck & Co., Inc.; West Point PA) Abstract TBA

 

5:30 PM - 6:30 PM - Discussion

 

END OF DAY 

Friday, February, 25, 2005

 

8:00 AM – 9:00 AM – REGISTRATION

 

8:00 AM – 5:00 PM - EXHIBITS

 

9:00 AM - 9:45 AM

Pharmacotransport: Impact on the Drug Development Process (Willy Roth, Boehringer Ingelheim Pharma, GmbH & Co. KG, Biberach/Riss, GERMANY) Any drug ideally contains a message for a specific receptor/effector unit in the body to which it ultimately needs to be transported (Pharmacotransport) to exert its pharmacological effect. Recent knowledge about uptake- and efflux mechanisms for drugs and metabolites and their interplay support the evaluation of drug concentration profiles also as a function of drug transport processes at the interface to different tissues. Drug / metabolite transport characteristics may substantially influence the interpretation of non-clinical drug safety studies and thus influence the design and the interpretation of clinical investigations. The presentation will focus on two central aspects in drug development: drug safety and drug efficacy. Based on available literature data and so far unpublished experiments in drug development, examples will be discussed, how information about drug transport properties (pharmacotransport) together with pharmacokinetic knowledge may have significant impact on the interpretation of non-clinical drug safety results and how this type of information may also aid the interpretation of clinical studies.

                                   

9:45 AM - 10:30 AM

Factors Based on Transporters that Cause Alteration of Absorption and Disposition of Drug Candidates During Discovery and Development Stage (Takayoshi Yoshikawa , Shionogi & Co. Ltd.; Osaka, JAPAN) Factors based on transporters that cause alteration of absorption, distribution and disposition of drug candidates will be summarized. Especially, in drug discovery and development stage, some topics for intestinal absorption, distribution, brain efflux and renal excretion of drug and drug candidates caused by some transporters will be introduced with some pharmacokinetic and pharmacological results.

 

10:30 AM - 10:45 AM – BREAK

 

10:45 AM - 11:30 AM

Use of KO Mice, Transporter Expression Systems, Human Tissue and Cells for Evaluation of Contributed Transporters (Sonia M. de Morais, Pfizer Global Research and Development Groton Laboratories; Groton, CT) The pharmaceutical companies are being challenged to conduct the Discovery process more efficiently and at lower cost.  To achieve this, it is imperative that the tools and knowledge available to understand drug disposition mediated by transporters are utilized wisely.  Numerous transfected cell lines and some genetically modified mice are now available to understand these processes. This presentation will review the existing in vitro and in vitro tools and propose some strategies for the implementation of screens and decision-making early in the discovery process.

 

11:30 AM -12:15 PM - Discussion  

 

END OF CONFERENCE

 

 

POSTER PRESENTATIONS:

 

Poster Presentations are always encouraged.  Please submit your poster abstract for approval by the organizing board by January 30^th.  Poster size should be no larger than 3 feet high by 7 feet long.  Abstracts of posters will be included in the participant binder and in the ISE website.  There is no formal poster presentation scheduled.  All posters will remain displayed throughout the conference.  Please be prepared to display your poster during registration on or before the first session begins on Wednesday, February 23^rd  Poster presenters will have ample time for discussion during breaks and the Welcome reception. Submit posters abstracts for approval to Nola Mahaney, VP, Operations; ISE, Inc.; 5707 Calverton Street, Suite 2C; Baltimore, MD 21228 or fax at (410) 869-9560 or email file attachment to nola@isciencex.com.  Approved poster presenters are responsible for completing a conference attendance registration form and payment of fee (visit www.isciencex.com/register.htm) and for the shipping of the poster itself.  Please contact Nola Mahaney for any questions or concerns.  Please refer to “Travel Information” for hotel address and shipping information.

 

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Travel Information

The Symposium venue, the San Diego Marriott Mission Valley is conveniently located at Interstate 8. Exit Qualcomm Way to Rio San Diego Drive, just ½ mile west of Qualcomm Stadium. Located minutes from Qualcomm stadium, San Diego Zoo, Sea World©, and the San Diego Mission. A number of restaurants, shops and services are also nearby.  Please contact the hotel for further information.

 

Hotel Information

A limited number of rooms have been reserved at The San Diego Marriott Mission Valley, 8757 Rio San Diego Drive; San Diego, CA, 92108 USA, at a reduced conference rate of US $129.00 per night (plus applicable taxes-single occupancy).  Please make your hotel reservation directly by telephone at (800) 842-5329, (619) 692-3800, fax (619) 692-0769 or www.marriott.com.  Please ask for “ETS-2005” block for ISE, Inc.

 

Payment

Payment may be made by check or credit card.  Checks should be made in US $, payable to Institute for Scientific Exchange, Inc.  Mail to: ISE, Inc., 5707 Calverton Street, Suite 2C, Baltimore, MD 21228, USA

 

Cancellation Policy

All cancellations are subjected to a $250.00 cancellation fee. Longer than 30 days, 100% refund. Less than 30 days, no refund but registration may be transferred to another person.  All refund requests must be in writing.  All refunds will be issued after the meeting has occurred. No refunds requests will be accepted after January 21, 2005. Please submit cancellation and refund requests including transferring of registration to:

 

Fax:  410-869-9560

E-mail: nola@isciencex.com

Deadline: January 21, 2005

 

Email to nola@isciencex.com or mail/fax completed form with remittance to: ISE, Inc. 5707 Calverton Street, Suite 2C, Baltimore, MD 21228, USA; FAX No:  (410) 869-9560.  Payment may be made by check in US$, payable to Institute for Scientific Exchange, Inc. or by credit card.

 

Payment Method:  Check, Credit Card (VISA, MASTER CARD, AMERICAN EXPRESS)

 

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CTDD-2005 Registration:  US$1500.00__________

ETS-2005:                             US$1500.00__________

 

SPECIAL DISCOUNT FOR BOTH US$2000.00_____

CTDD-2005 is being held in conjunction with ETS-2005. ETS-2005 - 5th International Conference on Early Toxicity Screening: Strategies and Approaches for Toxicity Screening In Drug Discovery and Development; February 21-23, 2005 also at the San Diego Mission Valley Marriott.  Please join ISE, Inc. for both events and receive a discount.

 

 

 

Exhibitors:                             US $2000.00________

 

Academic/Government participants will receive a 50% discount. 

 

Contact Nola Mahaney for Exhibitor or Sponsorship Opportunities at nola@isciencex.com, or phone (410) 869-9166); or visit www.isciencex.com/exhibitors .

 

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