The Laboratory Robotics Interest Group
Mid Atlantic Chapter
November 2008 Meeting
2008 LRIG Workshop on ADMET/PK
Date: Wednesday, November 12, 2008
Place:
Crowne Plaza Somerset-Bridgewater ,
110 Davidson Avenue, Somerset NJ 08873
Phone:
1-877-270-1393
Itinerary: Social Period w/appetizers: 4:30 to 5:45 pm
Dinner: 5:45 to 6:30 PM
Presentations: 6:30 to 9:00 PM
Registration: We have an on-line registration service at <https://www.lab-robotics.org/member/meetings.asp?rid=1>.
Food and refreshments will be available FREE OF CHARGE
during the Social Period.
There
is always a Job posting board at the social. Please encourage your
recruiters to give you material to post and distribute.
Openings may be also posted at
https://www.lab-robotics.org/forum/default.asp?CAT_ID=2
There is no fee to attend the meeting.
Click here to view the PDF file of the agenda.
Presentation: Practical human PK prediction approaches using in silico,
in vitro and in vivo animal data
Dr. Handan He
Director and Head of Preclinical PK/PD
Novartis Pharmaceuticals Corporation.
The accurate prediction of human pharmacokinetic parameters based on early in
vitro and in vivo preclinical data remains a major challenge in drug
development. Various approaches have been published, each having their own
advantages and limitations. The predictability of these approaches varies
significantly and is largely dependent on individual compound properties and
interspecies differences. There is an increased focus to use more mechanistic
approaches, e.g. physiologically based pharmacokinetics, in addition to
empirical methods, e.g. allometric scaling. Although mechanistic models (PBPK)
allow an understanding of the effect physiological variables on pharmacokinetic
parameters, the successful development and implementation of routine PBPK models
is still limited, as significant experience, and resource intensive data are
often required,. Thus, allometric scaling approaches have remained and expanded
their uses as valuable tools in drug development. Of course, many theories and
different approaches have been proposed for improving the predictive performance
of allometry for CL, Vss and t1/2. Besides prediction of PK parameters, attempts
have also been made to predict plasma concentration profiles. This presentation
is to share our experience with you in predicting human PK parameters, e.g. CL,
Vss, t1/2, ka and F% as well as oral PK profiles in plasma and tissues. To
predict human CL, it is suggested to use multiple approaches to assess
prediction confidence, e.g. IVIVC using microsomal or hepatocyte data,
allometric scaling (rule of exponent), single species allometric scaling and
fraction unbond corrected intercept method (FCIM). To predict Vss, 3 multiple
species approaches e.g. Oie-Tozer, allometric scaling (1-3 species) and PBPK
will be discussed. Moreover, many approaches for t1/2, ka, F% will also be
recommended. In terms of PK profile prediction, PBPK, Wajima and
twocompartmental allometric scaling will be among the choices. This presentation
will not only describe scaling techniques using Novartis examples, but also
highlight how to address interspecies differences to improve prediction
confidence in the anticipation of human doses
Presentation:
Improving Candidate Quality Through the Prediction of Clinical Outcome
Dr. Simon Thomas
Head of Scientific Computing
Cyprotex Discovery Ltd
Despite ever-increasing discovery and preclinical budgets, and data generation
for new compounds, most new compounds that enter clinical trials fail in Phases
I or II. In essence, this is due to the difficulty of predicting fundamental
pharmacological behaviour in human a priori. This prediction requires the
combination of data from in vitro efficacy, ADME and toxicity screens, as well
as the results obtained in animal models. The combination of all relevant data
is necessary to help to predict the clinical outcome of the administration of a
novel compound, and to guide lead optimisation and candidate selection. One
means of achieving this combination of data is by simulation modelling.
Physiologically-based pharmacokinetic (PBPK) modelling is becoming a widely
established means of predicting pharmacokinetics, including the crucial aspects
of target and non-target tissue exposure. Combining tissue dosimetry predictions
from PBPK modelling with the modelling of drug action at target sites enables
lead optimisation to be guided rationally by optimising on in vivo therapeutic
effect. Incorporating toxicity data in the same manner increases the value of
the approach. I shall present results of an ongoing study on PK/PD modelling of
the statins, a group of compounds that reduce plasma LDL-cholesterol levels by
inhibition of HMG-CoA reductase, an enzyme of the cholesterol synthesis pathway.
I shall describe the use of ADME data generated in HT in vitro screens, activity
data generated in receptor and cell-based in vitro screens, and PK and response
data from preclinical species (and even from humans for the special case of
e-too?drug development). The interplay between activity and ADME/PK data will
be discussed, as will the continuing challenge of developing cost-effective
alternatives to in vivo animal PK screens.
Presentation:
Formulation approaches in addressing PK Related Issues
Dr. Hong Wen
Pharmaceutical Development
Novartis Pharmaceuticals Corporation.
For each compound, its PK profile
is affected by not only its physico-chemical and biopharmaceutical properties,
but also the formulation design. Based on drug solubility and permeability,
drugs have been classified into four classes. For those drugs with poor water
solubility or low permeability, lots of research has been done to improve their
bioavailability. Considering the Lead compound screen process, most new
compounds are poorly water soluble, and most pharmaceutical development are
focusing on improving their dissolution in the human GI tract. Besides, some
drugs with narrow adsorption window, i.e. narrow adsorption region in human GI
tract, some special delivery systems can help to improve the bioavailability by
overcoming the short transit time of drug in those specific GI regions.
Furthermore, some special delivery system like controlled release formulations
can be useful for those drugs with short half, or narrow therapeutic window.
Those controlled release formulation can improve patient compliance, as well as
reduce side effects related to high Cmax.
Presentation: R&D
Knowledge Assessment Shapes Scientific Information Strategy
Bob Oara
Managing Partner
ResultWorks, LLC
At the highest level,
Pharmaceutical R&D is supported by a number of formal and well developed
scientific information systems that are carefully managed. These systems and the
inherent scientific knowledge they support are quite visible to upper
management. Yet over time, R&D communities employ of a variety of informal
systems from spreadsheets to commercial systems that are often implemented
nder the radar?of the formal IT support channels. Several pharmaceutical
companies recently undertook an effort to assess the scientific information
systems being used throughout their organizations, including formal as well as
informal systems. They contracted with ResultWorks to perform a collaborative
assessment of R&D knowledge assets from discovery through early development.
These projects lead to better prioritization of R&D scientific information
system needs, key knowledge assets and a roadmap of system initiatives for the
future. This presentation will outline the business problems recognized by
several clients, the approach undertaken to uncover and catalog scientific
knowledge assets and the resulting strategic roadmap that became the foundation
for guiding R&D scientific information system investments.
The
Menu!
Little Italy
Fresh Baked Garlic Bread, Flatbreads, Assorted Rolls,
Breadsticks
Caesar Salad
Mozzarella Capresa
Freshly Sliced Roma Tomatoes, Roasted Red Peppers, Sun-dried Tomatoes, Fresh
Mozzarella and Topped with a Drizzle of Olive Oil, Garlic and Fresh Basil
Pasta eFagioli
A Robust Soup with Pasta and Beans
Grilled Chicken with Pesto Sauce, Sundried Tomatoes and
Provolone Cheese
Sole a la Nina
Fillet of Sole with Sun Dried Tomatoes, Basil and Fresh Plum Tomatoes
Bistecca Giambotta
Grilled Sliced Steak Served with Fried Potatoes, Baked Mushrooms, Onions, Hot
and Sweet Peppers
Pasta Station
Radiatorre, and Penne
served with Marinara or Pink Vodka Sauce
Eggplant Rollitini
Served with Saut嶪d Zucchini with Onions and Red Sauce and
Risotto
Dessert
Ricotta Cheesecake
Miniature Italian Pastries and Cookies
Assorted Sodas and bottled water
Freshly Brewed Columbian Coffee, Decaffeinated Coffee and
Herbal Tea
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Interest Group homepage at https://www.lab-robotics.org
