# Pharmacokinetics in Toxicology Research

Save this PDF as:

Size: px
Start display at page:

## Transcription

1 Pharmacokinetics in Toxicology Research Center for Human Health Assessment A Course on Physiologically Based Pharmacokinetic (PBPK) Modeling and Risk Assessment February 11 February 15, 2008 Copyright 2008 by The Hamner Institutes for Health Sciences. May not be reproduced without permission

2 External exposure Pharmacokinetics Absorbed dose Target dose Tissue interaction Early effect Pharmacodynamics Adverse effect Disease/injury

3 Pharmacokinetics Studies of the change in chemical distribution over time in the body Explores the quantitative relationship between Absorption, Distribution, Metabolism, and Excretion of a given chemical Classical models Data-based, empirical compartments Describes movement of chemicals with fitted rate constants Physiologically-based models: Compartments are based on real tissue volumes Mechanistically based description of chemical movement using tissue blood flow and simulated in vivo transport processes.

4 Example of Simple Kinetic Model: One-compartment model with bolus dose Dose Volume? Purpose: In a simple (1-compartment) system, determine volume of distribution Terminology: Compartment = a theoretical volume for chemical Steady-state = no net change of concentration Bolus dose = instantaneous input into compartment Method: 1. Dose: Add known amount (A) of chemical 2. Experiment: Measure concentration of chemical (C) in compartment 3. Calculate: A compartmental Volume (V)

5 Example of Simple Kinetic Model: One-compartment model with bolus dose Basic assumption: Well stirred, instant equal distribution within entire compartment Volume of distribution = A/C In this classical model, V is an operational volume V depends on site of measurement This simple calculation only works IF: Compound is rapidly and uniformly distributed The amount of chemical is known The concentration of the solution is known. What happens if the chemical is able to leave the container?

6 Describing the Rates of Chemical Processes - 1 Chemical in the System Rate equations: Describe movement of chemical between compartments The previous example had instantaneous dosing Now, we need to describe the rate of loss from the compartment Zero-order process: rate is constant, does not depend on chemical concentration rate = k x C 0 = k First-order process: rate is proportional to concentration of ONE chemical rate = k x C 1

7 Describing the Rates of Chemical Processes - 2 Chemical Systems Second-order process: rate is proportional to concentration of both chemicals Rate = k x C 1 x C 2 Saturable processes*: Rate is dependent on interaction of two chemicals One reactant, the enzyme, is constant Described using Michaelis-Menten* equation Rate = (V max x C) / ( C + K m ) 10 M-M kinetics *Michaelis-Menten kinetics can describe: Metabolism Carrier-mediated transport across membranes Excretion Rate C

8 1-Comp model with bolus dose and 1 st order elimination Dose Conc? Concentration; Purpose: Examine how concentration changes with time Mass-balance equation (change in C over time): -da/dt=-k e x A, or -dc/dt=-k e x C where k e = elimination rate constant - Rearrange and integrate above rate equation C = C 0 x e -ke t, or ln C = ln C 0 -k e t Half-life (t 1/2 ): - to reduce concentration by 50% -replace C with C 0 /2 and solve for t t 1/2 = (ln 2)/k e = 0.693/k e

9 1-Comp model with bolus dose and 1 st order elimination Dose Conc Clearance: volume cleared per time unit - if k e = fraction of volume cleared per time unit, k e = CL/V (CL=ke ke*v) Calculating Clearance using Area Under the Curve (AUC): AUC = average concentration - integral of the concentration - C dt 10 CL = volume cleared over time (L/min) da/dt = - k e A = -k e V C da/dt = - CL C da = - CL C dt Dose = CL AUC CL = Dose / AUC 5 0 AUC

10 1-Comp model with continuous infusion and 1st order elimination Calculating Clearance at Steady State: At steady state, there is no net change in concentration: dc/dt = k 0 /V k e C = 0 Rearrange above equation: k 0 /V = k e C ss Steady State Since CL = k e V, CL = k 0 /C ss

11 2-Comp model with bolus dose and 1 st order elimination k k 21 k e Calculating Rate of Change in Chemical: Central Compartment (C1): dc1/dt = k 21 C 2 - k 12 C 1 - k e C 1 Peripheral (Deep) Compartment (C2): dc2/dt = k 12 C 1 - k 21 C 2

12 Linear: Linear and Non-linear Kinetics All elimination and distribution kinetics are 1 st order Double dose double concentration AUC Non-linear: At least one process is NOT 1 st order Dose No direct proportionality between dose and compartment concentration

13 PBPK Models Building a PBPK Model: 1. Define model compartments Represent tissues 2. Write differential equation for each compartment 3. Assign parameter values to compartments Compartments have defined volumes, blood flows 4. Solve equations for concentration Numerical integration software (e.g. Berkeley Madonna, ACSL) Venous side Chemical in air Lungs Other Fat tissues Liver Elimination Simple model for inhalation Arterial side

14 PBPK Model Compartment Types - Storage compartment Chemical in air QT CVT QT CA Same as 1-compartment model with continuous infusion Lungs Other Fat tissues Liver Rate in = Q T C A where Q T = tissue blood flow, C A = arterial blood conc Elimination Rate out = Q T C VT = Q T C T /P T where C VT = conc in tissue blood, C T = conc in tissue, P T = partition coefficient Assume Well-stirred compartment, so that, C VT = C T /P T

15 PBPK Model Compartment Types - Storage compartment Chemical in air QT CVT QT CA Same as 1-compartment model with continuous infusion Lungs Other Fat tissues Liver Calculating Change in Amount: Change in amount = rate in rate out E lim ination da/dt = Q T x (C A C T /P T ) dc/dt = Q T x (C A C T /P T ) /V C A Dose C VT

### Constructing PK Models

Constructing PK Models Interpretation of biomonitoring data using physiologically based pharmacokinetic modeling Center for Human Health Assessment September 25-29, 29, 2006 Pharmacokinetics Studies of

### IV solutions may be given either as a bolus dose or infused slowly through a vein into the plasma at a constant or zero-order rate.

د.شيماء Biopharmaceutics INTRAVENOUS INFUSION: IV solutions may be given either as a bolus dose or infused slowly through a vein into the plasma at a constant or zero-order rate. The main advantage for

### Day 3 Exercise 2 Parameter Optimization and Sensitivity Analysis: An Example Using a PBPK Model for Warfarin. April 19-23, 2010.

Day 3 Exercise 2 Parameter Optimization and Sensitivity Analysis: An Example Using a PBPK Model for Warfarin A Course on Physiologically Based Pharmacokinetic (PBPK) Modeling and In Vitro to In Vivo Extrapolation

### PHAR 7633 Chapter 21 Non-Linear Pharmacokinetic Models

Student Objectives for this Chapter PHAR 7633 Chapter 21 Non-Linear Pharmacokinetic Models To draw the scheme and write the differential equations for compartmental pharmacokinetic models with non-linear

### 1: CLINICAL PHARMACOKINETICS

: CLINICAL PHARMACOKINETICS General overview: clinical pharmacokinetics, 2 Pharmacokinetics, 4 Drug clearance (CL), 6 Volume of distribution (Vd), 8 The half-life (t½), 0 Oral availability (F), 2 Protein

### PHAR 7633 Chapter 19 Multi-Compartment Pharmacokinetic Models

Student Objectives for this Chapter PHAR 7633 Chapter 19 Multi-Compartment Pharmacokinetic Models To draw the scheme and write the differential equations appropriate to a multi-compartment pharmacokinetic

### AP CHEMISTRY CHAPTER REVIEW CHAPTER 11: RATE OF REACTION

AP CHEMISTRY CHAPTER REVIEW CHAPTER 11: RATE OF REACTION You should understand the definition of reaction rate, as well as how rates might be measured in a laboratory setting. You should know the difference

### Study (s) Degree Center Acad. Period. 1201 - Grado de Farmacia FACULTY OF PHARMACY 3 Annual 1211 - PDG Farmacia-Nutrición Humana y Dietética

COURSE DATA Data Subject Código 34081 Name Biopharmacy and Pharmacokinetics Cycle Grade ECTS Credits 10.5 Curso académico 2014-2015 Study (s) Degree Center Acad. Period year 1201 - Grado de Farmacia FACULTY

### Physical Chemistry. Lecture 4 Introduction to chemical kinetics

Physical Chemistry Lecture 4 Introduction to chemical kinetics Thermodynamics and kinetics Thermodynamics Observe relative stability of states Energy differences Static comparisons of states Kinetics Observe

### Statistics and Pharmacokinetics in Clinical Pharmacology Studies

Paper ST03 Statistics and Pharmacokinetics in Clinical Pharmacology Studies ABSTRACT Amy Newlands, GlaxoSmithKline, Greenford UK The aim of this presentation is to show how we use statistics and pharmacokinetics

### Introduction to Pharmacokinetic/ Pharmacodynamic Modeling: Concepts and Methods. Alan Hartford Agensys, Inc. An Affiliate of Astellas Pharma Inc

Introduction to Pharmacokinetic/ Pharmacodynamic Modeling: Concepts and Methods Alan Hartford Agensys, Inc. An Affiliate of Astellas Pharma Inc Outline Introduction to Pharmacokinetics Compartmental Modeling

### Lecture 11 Enzymes: Kinetics

Lecture 11 Enzymes: Kinetics Reading: Berg, Tymoczko & Stryer, 6th ed., Chapter 8, pp. 216-225 Key Concepts Kinetics is the study of reaction rates (velocities). Study of enzyme kinetics is useful for

### Chapter 12 - Reaction Kinetics

Chapter 12 - Reaction Kinetics In the last chapter we looked at enzyme mechanisms. In this chapter we ll see how enzyme kinetics, i.e., the study of enzyme reaction rates, can be useful in learning more

### For enzymes, kinetic information is useful for understanding how metabolism is regulated and how it will occur under different conditions.

Introduction to Enzyme kinetics Why study kinetics? Kinetic information is useful for examining possible mechanisms for the reaction. This is true for all types of reactions; kinetic principles are used

### Drug Prescribing in Kidney Disease: Initiative for Improved Dosing

Drug Prescribing in Kidney Disease: Initiative for Improved Dosing Effects of impaired kidney function on drug pharmacokinetics and pharmacodynamics Section Leaders: William Bennett and Domenic Sica Passage

### Dynamic Process Modeling. Process Dynamics and Control

Dynamic Process Modeling Process Dynamics and Control 1 Description of process dynamics Classes of models What do we need for control? Modeling for control Mechanical Systems Modeling Electrical circuits

### Questions and Answers for Health Care Providers: Renal Dosing and Administration Recommendations for Peramivir IV

Questions and Answers for Health Care Providers: Renal Dosing and Administration Recommendations for Peramivir IV The purpose of this document is to provide additional clarification to the existing information

### Nursing 113. Pharmacology Principles

Nursing 113 Pharmacology Principles 1. The study of how drugs enter the body, reach the site of action, and are removed from the body is called a. pharmacotherapeutics b. pharmacology c. pharmacodynamics

### Plasma Drug Concentration Time Profile Plotting Data

UNIT 2 PHARMACOKINETICS-BASIC CONSIDERATIONS Plasma Drug Concentration Time Profile Plotting Data S. SANGEETHA., M.PHARM., (Ph.d) Department of Pharmaceutics SRM College of Pharmacy SRM University INTRODUCTION

### QSAR. The following lecture has drawn many examples from the online lectures by H. Kubinyi

QSAR The following lecture has drawn many examples from the online lectures by H. Kubinyi LMU Institut für Informatik, LFE Bioinformatik, Cheminformatics, Structure independent methods J. Apostolakis 1

### A Peak at PK An Introduction to Pharmacokinetics

Paper IS05 A Peak at PK An Introduction to Pharmacokinetics Hannah Twitchett, Roche Products Ltd, Welwyn Garden City, UK Paul Grimsey, Roche Products Ltd, Welwyn Garden City, UK ABSTRACT The aim of this

### Pharmacology skills for drug discovery. Why is pharmacology important?

skills for drug discovery Why is pharmacology important?, the science underlying the interaction between chemicals and living systems, emerged as a distinct discipline allied to medicine in the mid-19th

### Lecture 3: Enzyme kinetics

Computational Systems Biology Lecture 3: Enzyme kinetics Fri 19 Jan 2009 1 Images from: D. L. Nelson, Lehninger Principles of Biochemistry, IV Edition, W. H. Freeman ed. A. Cornish-Bowden Fundamentals

### DOSE-EFFECT RELATIONSHIP

DOSE-EFFECT RELATIONSHIP A fundamental principle of pharmacology is that the intensity of effect produced by a drug is a function of the quantity of drug administered (or the concentration of the drug

### Reaction Rates and Chemical Kinetics. Factors Affecting Reaction Rate [O 2. CHAPTER 13 Page 1

CHAPTER 13 Page 1 Reaction Rates and Chemical Kinetics Several factors affect the rate at which a reaction occurs. Some reactions are instantaneous while others are extremely slow. Whether a commercial

### C.4 Applications of Differential Equations

APPENDIX C Differential Equations A39 C.4 Applications of Differential Equations Use differential equations to model and solve real-life problems. EXAMPLE 1 Modeling Advertising Awareness The new cereal

### CHEM 116 Rates of Reaction

UMass Boston, Chem 6 CHEM 6 Rates of Reaction FSG is cancelled Lecture Prof. Sevian today (Oct 4) in order to keep both FSG sections at the same pace (since there was no school yesterday) Today s agenda

### PHAR 7633 Chapter 22 Non-Linear Regression Analysis of Pharmacokinetic Data Individual Data and Population Analysis

PHAR 7633 Chapter 22 Non-Linear Regression Analysis of Pharmacokinetic Data Individual Data and Population Analysis Student Objectives for this Chapter Understand the use of computer programs such as Boomer

### PRINCIPLES OF PHARMACOKINETICS

Harvard-MIT Division of Health Sciences and Technology HST.151: Principles of Pharmocology Instructor: Prof. Carol Walsh HST-151 1 PRINCIPLES OF PHARMACOKINETICS Learning Objectives: 1. Describe the physicochemical

### Absorption of Drugs. Transport of a drug from the GI tract

Absorption of Drugs Absorption is the transfer of a drug from its site of administration to the bloodstream. The rate and efficiency of absorption depend on the route of administration. For IV delivery,

### Biomedical Optics Theory

Introduction Biomedical Optics Theory Diffuse reflectance spectroscopy (DRS) and Laser Doppler Flowmetry (LDF) are booth optical techniques that can quantify a number of microcirculatory parameters. Prof

### CLOSED LOOP MODEL FOR GLUCOSE INSULIN REGULATION SYSTEM USING LABVIEW

CLOSED LOOP MODEL FOR GLUCOSE INSULIN REGULATION SYSTEM USING LABVIEW 1 P Srinivas 2 P.Durga Prasada Rao 1 Associate Professor, Department of EIE, VR Siddhartha Engineering College, Vijayawada, India Email:

### ( ) = ( ) = {,,, } β ( ), < 1 ( ) + ( ) = ( ) + ( )

{ } ( ) = ( ) = {,,, } ( ) β ( ), < 1 ( ) + ( ) = ( ) + ( ) max, ( ) [ ( )] + ( ) [ ( )], [ ( )] [ ( )] = =, ( ) = ( ) = 0 ( ) = ( ) ( ) ( ) =, ( ), ( ) =, ( ), ( ). ln ( ) = ln ( ). + 1 ( ) = ( ) Ω[ (

### DIVISION OF HUMAN NUTRITION

DIVISION OF HUMAN NUTRITION Example EXAM 2011 - HNE-23306 Nutrition & Pharmacology Date : Place : Explanation : This exam consists of: **** open problems on pharmacokinetics (normally 2-3) *****series

### BIOAVAILABILITY & BIOEQUIVALENCE TRIALS

BIOAVAILABILITY & BIOEQUIVALENCE TRIALS Shubha Rani,, Ph.D. Technical Director & Head-Biometrics and Data Management Synchron Research Services Pvt. Ltd. Ahmedabad 380 054 drshubha@synchronresearch.com

### Chapter 12 - Chemical Kinetics

Chapter 1 - Chemical Kinetics 1.1 Reaction Rates A. Chemical kinetics 1. Study of the speed with which reactants are converted to products B. Reaction Rate 1. The change in concentration of a reactant

### 1/17/2013. Dose Response and Concentration Response Analysis of Drug Effects

Dose Response and Concentration Response Analysis of Drug Effects Juan J. L. Lertora. M.D., Ph.D. IH Clinical Center January 17, 213 1 DOSE-EFFECT RELATIOSHIP The intensity and duration of a drug s effect(s)

### Fexinidazole a new oral treatment for sleeping sickness update of development

Fexinidazole a new oral treatment for sleeping sickness update of development SMe O 2 Me CH 2 O Antoine TARRAL Olaf Valverde Séverine Blesson Clélia Bardonneau Wilfried Mutumbo September 2011 Fexinidazole

### Reaction of Blue Food Dye with Bleach

Exercise 2 Reaction of Blue Food Dye with Bleach 2 Introduction In the experiment, you will study the rate of the reaction of FD&C Blue #1 (Blue #1 is denoted by E number E133 in food stuff) with sodium

### Enzymes. Enzymes are characterized by: Specificity - highly specific for substrates

Enzymes Enzymes are characterized by: Catalytic Power - rates are 10 6-10 12 greater than corresponding uncatalyzed reactions Specificity - highly specific for substrates Regulation - acheived in many

### Exposure Modeling. Interpretation of biomonitoring data using physiologically based pharmacokinetic modeling. Centers for Human Health Assessment

Exposure Modeling Interpretation of biomonitoring data using physiologically based pharmacokinetic modeling Centers for Human Health Assessment September 25-29, 2006 Exposure assessment Emission Inhalation

### Particle dissolution and solute absorption: Key factors in the pulmonary kinetics of inhaled drugs

Particle dissolution and solute absorption: Key factors in the pulmonary kinetics of inhaled drugs Per Gerde Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden and Inhalation

### Chemical Kinetics. Reaction Rate: The change in the concentration of a reactant or a product with time (M/s). Reactant Products A B

Reaction Rates: Chemical Kinetics Reaction Rate: The change in the concentration of a reactant or a product with time (M/s). Reactant Products A B change in number of moles of B Average rate = change in

### SWAT INPUT DATA:.GW CHAPTER 24

CHAPTER 24 SWAT INPUT DATA:.GW SWAT partitions groundwater into two aquifer systems: a shallow, unconfined aquifer which contributes return flow to streams within the watershed and a deep, confined aquifer

### Review. Complex drug interactions; renal impairment; physiologically-based pharmacokinetic modeling (PBPK) Key words:

BIOPHARMACEUTICS & DRUG DISPOSITION Biopharm. Drug Dispos. 33: 99 110 (2012) Published online 4 March 2012 in Wiley Online Library (wileyonlinelibrary.com).1771 Review Utility of a physiologically based

### Basic Concepts of Pharmacokinetics

Basic Concepts of Pharmacokinetics Achiel Van Peer, Ph.D. Clinical Pharmacology 1 Some introductory Examples 2 15 mg of Drug X in a slow release OROS capsule administered in fasting en fed conditions in

### Volume of Distribution

1 Volume of Distribution Nick Holford Dept Pharmacology & Clinical Pharmacology University of Auckland, New Zealand 2 Objectives Learn the definition of volume of distribution Understand the physiological

### Exercise Day 3-13 A PBPK Model for Methyl Mercury

Exercise Day 3-13 A PBPK Model for Methyl Mercury Interpretation of biomonitoring data using physiologically based pharmacokinetic modeling Center for Human Health Assessment September 25-29, 29, 2006

### 1. [20 pts] Find an integrating factor and solve the equation y 3y = e 2t. Then solve the initial value problem y 3y = e 2t, y(0) = 3.

22M:034 Engineer Math IV: Differential Equations Midterm Exam 1 October 2, 2013 Name Section number 1. [20 pts] Find an integrating factor and solve the equation 3 = e 2t. Then solve the initial value

### Enzyme Kinetics: Velocity

ENZYME KINETICS: The rate of the reaction catalyzed by enzyme E A + B P is defined as -Δ[A] or -Δ[B] or Δ[P] Δt Δt Δt A and B changes are negative because the substrates are disappearing P change is positive

### L 2 : x = s + 1, y = s, z = 4s + 4. 3. Suppose that C has coordinates (x, y, z). Then from the vector equality AC = BD, one has

The line L through the points A and B is parallel to the vector AB = 3, 2, and has parametric equations x = 3t + 2, y = 2t +, z = t Therefore, the intersection point of the line with the plane should satisfy:

### Equations for Primary FRCA

Equations for Primary FA Pharmacology : concentration t: time Bioavailability Bioavailab ility AU AU OAL IV AU: area under concentration time curve Exponential Function d d or K. dt dt e.78 or 0. 37 e

### A Framework for the development and application of biological monitoring guidance values

A Framework for the development and application of biological monitoring guidance values Len Levy, Ruth Bevan, Greet Schoeters, Roel Smolders, Juergen Angerer, Ovnair Sepai, Kate Jones & John Cocker Institute

### Guideline on the investigation of drug interactions

21 June 2012 CPMP/EWP/560/95/Rev. 1 Corr. 2** Committee for Human Medicinal Products (CHMP) Discussion in the Efficacy Working Party (EWP) June/October 1996 February 1997 Transmission to the CPMP March

### Determinants of Blood Oxygen Content Instructor s Guide

Determinants of Blood Oxygen Content Instructor s Guide Time to Complete This activity will take approximately 75 minutes, but can be shortened depending on how much time the instructor takes to review

### How Long Does It Take a Person to Sober Up? Some Mathematics and Science of DUI

Activities for students Bente B. Winston and Matthew T. Zunker How Long Does It Take a Person to Sober Up? Some Mathematics and Science of DUI Activities for Students appears six times each year in Mathematics

### The Rate and Extent of Calcium Bioavailability from Two Oral Dosage Forms in Rats

Gen. Physiol. Biophys. (1985), 4, 531-536 531 The Rate and Extent of Calcium Bioavailability from Two Oral Dosage Forms in Rats M. ĎURISOVÁ 1, T. TRNOVEC 1, Š. BEZEK 1, Z. KÁLLAY 1 and M. ZEMÁNEK 2 1 Institute

### Teriflunomide is the active metabolite of Leflunomide, a drug employed since 1994 for the treatment of rheumatoid arthritis (Baselt, 2011).

Page 1 of 10 ANALYTE NAME AND STRUCTURE TERIFLUNOMIDE Teriflunomide TRADE NAME Aubagio CATEGORY Antimetabolite TEST CODE PURPOSE Therapeutic Drug Monitoring GENERAL RELEVANCY BACKGROUND sclerosis. The

### Drug Excretion. Renal Drug Clearance. Drug Clearance and Half-Life. Glomerular Filtration II. Glomerular Filtration I. Drug Excretion and Clearance

t/.drugexcretion AINTRAVENOUSDOSE 36848765430TIME(hours) t/ Drug Excretion Dr. Robert G. Lamb Professor Pharmacology & Toxicology Drug Excretion and Clearance Drug Excretion: is the movement of drug from

### Radiation Interactions with Matter: Energy Deposition

Radiation Interactions with Matter: Energy Deposition Biological effects are the end product of a long series of phenomena, set in motion by the passage of radiation through the medium. Image removed due

### Target Mediated Disposition

Population Approach Group in Europe June 10, 2011, Athens, Greece Modeling Drugs with Target Mediated Disposition Leonid Gibiansky QuantPharm LLC Introduction Target-Mediated Drug Disposition: Binding

### GT-020 Phase 1 Clinical Trial: Results of Second Cohort

GT-020 Phase 1 Clinical Trial: Results of Second Cohort July 29, 2014 NASDAQ: GALT www.galectintherapeutics.com 2014 Galectin Therapeutics inc. Forward-Looking Statement This presentation contains, in

### Biological importance of metabolites. Safety and efficacy aspects

Biological importance of metabolites Safety and efficacy aspects Bernard Walther Technologie Servier Biological importance of metabolites Safety testing of drug metabolites Bioanalytical strategy Structural

### STUDIES TO EVALUATE THE SAFETY OF RESIDUES OF VETERINARY DRUGS IN HUMAN FOOD: CARCINOGENICITY TESTING

VICH GL28 (SAFETY: CARCINOGENITICY) Revision (at Step 9) February 2005 For implementation at Step 7 STUDIES TO EVALUATE THE SAFETY OF RESIDUES OF VETERINARY DRUGS IN HUMAN FOOD: CARCINOGENICITY TESTING

### Biokinetic model of americium in the beagle dog. Salt Lake City, UT 84108-1218 (U.S.A.)

Biokinetic model of americium in the beagle dog A. Luciani 1, E. Polig 2, R. D. Lloyd 3, S. C. Miller 3 1 ENEA Radiation Protection Institute via dei Colli, 16 4136 Bologna, (Italy) 2 Forschungszentrum

### A First Course in Elementary Differential Equations: Problems and Solutions. Marcel B. Finan Arkansas Tech University c All Rights Reserved

A First Course in Elementary Differential Equations: Problems and Solutions Marcel B. Finan Arkansas Tech University c All Rights Reserved 1 Contents 1 Basic Terminology 4 2 Qualitative Analysis: Direction

### BioDMET Quick Start Guide. Biodistribution Simulation

BioDMET Quick Start Guide Biodistribution Simulation 1 Contents Introduction 3 Welcome to BioDMET 5 Applications Getting Started 7 System Requirements 8 The BioDMET Website 9 User Registration 10 Install

### STUDIES TO EVALUATE THE SAFETY OF RESIDUES OF VETERINARY DRUGS IN HUMAN FOOD: CARCINOGENICITY TESTING

VICH GL28 (SAFETY: CARCINOGENITICY) October 2002 For implementation at Step 7 - Final STUDIES TO EVALUATE THE SAFETY OF RESIDUES OF VETERINARY DRUGS IN HUMAN FOOD: CARCINOGENICITY TESTING Recommended for

### Diffusione e perfusione in risonanza magnetica. E. Pagani, M. Filippi

Diffusione e perfusione in risonanza magnetica E. Pagani, M. Filippi DW-MRI DIFFUSION-WEIGHTED MRI Principles Diffusion results from a microspic random motion known as Brownian motion THE RANDOM WALK How

### Clinical Study Synopsis for Public Disclosure

abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of the clinical

### CHAPTER 13 Chemical Kinetics: Clearing the Air

CHAPTER 13 Chemical Kinetics: Clearing the Air 13.1. Collect and Organize For the plot of Figure P13.1, we are to identify which curves represent [N O] and [O ] over time for the conversion of N O to N

### SAFETY PHARMACOLOGY STUDIES FOR HUMAN PHARMACEUTICALS S7A

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE SAFETY PHARMACOLOGY STUDIES FOR HUMAN PHARMACEUTICALS

### Medication Removal by Apheresis. Yanyun Wu, M.D., Ph.D. Yale University School of Medicine

Medication Removal by Apheresis Yanyun Wu, M.D., Ph.D. Yale University School of Medicine 1 Objectives Review basic pharmacokinetics and its relevance in drug removal by therapeutic apheresis (TPE) Review

### Modeling, Analysis, and Control of Dynamic Systems

Modeling, Analysis, and Control of Dynamic Systems Second Edition William J. Palm III University of Rhode Island John Wiley Sons, Inc. New York Chichester Weinheim Brisbane Singapore Toronto To Louise.

### Chemistry 212 EXAM 1 January 27, 2004

1 Chemistry 212 EXAM 1 January 27, 2004 _100 (of 100) KEY Name Part 1: Multiple Choice. (1 point each, circle only one answer, 1. Consider the following rate law: Rate = k[a] n [B] m How are the exponents

### Lafayette College Department of Civil and Environmental Engineering

Lafayette College Department of Civil and Environmental Engineering CE 321: Introduction to Environmental Engineering Fall 2010 Homework #4 SOLUTIONS Due: Monday, 9/27/10 SOLUTIONS 1. A completely mixed

### ENZYMES - EXTRA QUESTIONS

ENZYMES - EXTRA QUESTIONS 1. A chemical reaction has a G o = -60 kj/mol. If this were an enzyme-catalyzed reaction what can you predict about the kinetics? A. It will exhibit very rapid kinetics. B. It

### Pharmacotherapy in the Elderly. Judy MY Wong

Pharmacotherapy in the Elderly Judy MY Wong judywong@berkeley.edu Percentage of population with prescription and number of medication per individual increase with age Definitions Pharmacology: pharmakon

### The Kinetics of Atmospheric Ozone

The Kinetics of Atmospheric Ozone Ozone is a minor component of the earth s atmosphere (0.02 0.1 parts per million based on volume (ppm v )), yet it has a significant role in sustaining life on earth.

### Chemical Kinetics deals with rate (speed of chemical reactions ) how fast? Rate equation represents rate, which depends on various reactants

Kinetics 1 Kinetics Introduction Chemical Kinetics deals with rate (speed of chemical reactions ) how fast? Rate equation represents rate, which depends on various reactants Reaction mechanism is the details

### Introduction. MassDEP, Office of Research and Standards 1 Tetrachloroethylene

Summary of the Basis of Cancer Risk Values for Massachusetts Department of Environmental Protection (MassDEP) Office of Research and Standards January 22, 2014 Introduction In February 2012 the United

### Calculus for the Life Sciences I

Calculus for the Life Sciences I es Joseph M. Mahaffy, mahaffy@math.sdsu.edu Department of Mathematics and Statistics Dynamical Systems Group Computational Sciences Research Center San Diego State University

### Deterministic and Stochastic Modeling of Insulin Sensitivity

Deterministic and Stochastic Modeling of Insulin Sensitivity Master s Thesis in Engineering Mathematics and Computational Science ELÍN ÖSP VILHJÁLMSDÓTTIR Department of Mathematical Science Chalmers University

### Math 267 - Practice exam 2 - solutions

C Roettger, Fall 13 Math 267 - Practice exam 2 - solutions Problem 1 A solution of 10% perchlorate in water flows at a rate of 8 L/min into a tank holding 200L pure water. The solution is kept well stirred

### Fundamentals of Enzyme Kinetics

Fundamentals of Enzyme Kinetics Third edition by Athel Cornish-Bowden Universitats-und Landesbibliothek Bibliothek Biologie Schnittspahnstr. 10, 64287 Darmstadt lnv,nr. PORTLAND PRESS Preface to the Third

### Teacher s Guide. Chemicals & Human Health Website. Toxicology Activity

Teacher s Guide Chemicals & Human Health Website www.biology.arizona.edu/chh Toxicology Activity 1. Pre-test - Have the students the questions on the worksheet prior to visiting the website. This is just

### INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE S1A. Current Step 4 version

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE GUIDELINE ON THE NEED FOR CARCINOGENICITY STUDIES

### Physical Chemistry. Lecture 5 Theoretical chemical kinetics

Physical Chemistry Lecture 5 Theoretical chemical kinetics Chemical kinetics Understand the nature of reactions Predict reaction outcomes based on Reactants Conditions Requires integration of theory and

### Aging as a Risk Factor for Medication- Related Problems

Page 1 of 9 Quick jump to... Aging as a Risk Factor for Medication- Related Problems Mark H. Beers Today we are going to talk about why older people have more problems with medications in ways that younger

### Section 4. Toxicology

Section 4 Toxicology Occupational Health Any chemical you use incorrectly can result in over-exposure leading to adverse health effects immediately or in the future. All hazardous materials can be handled

### TEACHERS TOPICS Role of Protein Binding in Pharmacokinetics

TEACHERS TOPICS Role of Protein Binding in Pharmacokinetics Reza Mehvar, PhD School of Pharmacy, Texas Tech University Health Sciences Center Submitted January 3, 2005; accepted February 13, 2005; published

### Interface of Different Modules Within Simcyp

Data Entry & Input Interface of Different Modules Within Simcyp Flexibility for Variable Input & Added Complexity Compound Parameters Library Parameters LIVER GI TRACT KIDNEY 1. Whole Organ Clearance MPPGL

### PKPD modelling of the relationship between testosterone and PSA in patients with prostate cancer during treatment with leuprorelin

PAGE 2015, Crete PKPD modelling of the relationship between testosterone and PSA in patients with prostate cancer during treatment with leuprorelin What is the optimal testosterone level? Nelleke Snelder,

### Chapter 4 An Introduction to Chemical Reactions. An Introduction to Chemistry by Mark Bishop

Chapter 4 An Introduction to Chemical Reactions An Introduction to Chemistry by Mark Bishop Chapter Map Chemical Reaction A chemical change or chemical reaction is a process in which one or more pure substances

### NONCLINICAL EVALUATION FOR ANTICANCER PHARMACEUTICALS

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE NONCLINICAL EVALUATION FOR ANTICANCER PHARMACEUTICALS

### Uses of Derivative Spectroscopy

Uses of Derivative Spectroscopy Application Note UV-Visible Spectroscopy Anthony J. Owen Derivative spectroscopy uses first or higher derivatives of absorbance with respect to wavelength for qualitative

### IVIVC Methods and Applications in MR Product Development

IVIVC Methods and Applications in MR Product Development H. Rettig LLC www.ivivc.com Purpose of IVIVC and BCS Reduction of regulatory burden: IVIVC in lieu of additional in vivo experiments, leading to

### file:///biology Exploring Life/BiologyExploringLife04/

Objectives Compare and contrast ionic bonds and covalent bonds. Describe various ways to represent molecules. Summarize what happens in a chemical reaction. Key Terms ionic bond ion covalent bond molecule