Modeling Dynamic Gastrointestinal Fluid Transit as a Basis for Dissolution and Absorption
|
|
- Ezra Flynn
- 6 years ago
- Views:
Transcription
1 Modeling Dynamic Gastrointestinal Fluid Transit as a Basis for Dissolution and Absorption Duxin Sun, Ph.D. William I. Higuchi Collegiate Professor Department of Pharmaceutical Sciences Pharmacokinetics core Interdepartmental Program in Medicinal Chemistry Chemical Biology Program Comprehensive Cancer Center University of Michigan Ann Arbor, MI 48109
2 Oral Absorption is a Highly Complex Process Where GI Fluid Volume can Impact Oral Absorption
3 Compartmental Approach has Demonstrated Some Success in Predicting Oral Absorption Question: is there in vivo consideration of GI fluid volume?
4 Three Compartment Models Compared: Static Volume per Compartment Assumption Physiological Parameters for the Evaluated Intestinal Absorption Models Included in Simcyp (SC), GastroPlus (G+), and GI-Sim (GS) volume (ml) transit time (min) ph GI compartment SC b G+ GS SC G+ GS SC G+ GS Sjögren et al. In Silico Modeling of Gastrointestinal Drug Absorption: Predictive Performance of Three Physiologically Based Absorption Models Mol. Pharmaceutics, 2016, 13 (6), pp
5 Static Volume Assumption Leads Primarily to Mass Driven Absorption Primary terms for calculating absorption ACAT: Absorption ( dm dt ) = k i av (i) (C i L C i E ) ADAM: dc ent,n dt = 1 V ent,n (A diss,n ka n ) Rate of absorption differs between compartments Use of constant volumes leads to mass driven absorption calculations in each compartment This does not always characterize the real in vivo volume and its dynamic change, that influences absorption in the GI tract
6 Dynamic Fluid Model Reflects in vivo GI Volume Changes Traditional Approach Estimation V(n) Solid Dissolution M n (t) M n (t) Absorption Estimation Dissolution New Dynamic Volume Approach V n (t) Solid Dissolution M n (t) C n (t) Absorption Absorption Dissolution Absorption
7 Transit to Colon Dynamic Fluid Compartment Absorption and Transport Model Stomach Small Intestine Poster 09T0200 Alex Yu Drug M S M I1 M I2 M I3 M I,n M I30 Fluid V S V I1 V I2 V I3 V I,n V I30 Secretion/Absorption Systemic Circulation Defining Attributes Thirty small intestine compartments in series Forward and retrograde transit Net secretion in the stomach Secretion and absorption in duodenum Net absorption throughout the rest of small intestine
8 Impact of Unknown Volume in GI Tract Previously no available data of in vivo GI volume Generates uncertainty for basis in in vitro drug dissolution conditions and in vivo drug dissolution prediction. MRI study in human has provided total volume of stomach, small intestine, and colon, it did not provide volume of each segment of GI tract It did not provide dynamic volume change of each segment Dynamic change of GI fluid volume in each segment of GI tract is required to predict in vivo dissolution and concentration driven absorption There is no method to measure water secretion and absorption in the GI tract, which drives additional volume change Building a dynamic model needs to be based on extensive verification with clinical reference data
9 Measurement of Gastrointestinal (GI) Fluid Volume using MRI Mol Pharm Sep 2;11(9): doi: /mp500210c. Epub 2014 Aug 19. Quantification of gastrointestinal liquid volumes and distribution following a 240 ml dose of water in the fasted state. Mudie DM 1, Murray K, Hoad CL, Pritchard SE, Garnett MC, Amidon GL, Gowland PA, Spiller RC, Amidon GE, Marciani L.
10 Gastric liquid volume (ml) Stomach Fluid Transport Analysis mL water drink study Gastric liquid volumes n=12 (mean±sem) Time (min) Water Intake 240mL Secretion k ss Stomach V S Assume: Zero order secretion (constant) First order emptying Define terms based on best fit Emptying k qs Mol Pharm Sep 2;11(9): doi: /mp500210c. Epub 2014 Aug 19. Quantification of gastrointestinal liquid volumes and distribution following a 240 ml dose of water in the fasted state. Mudie DM 1, Murray K, Hoad CL, Pritchard SE, Garnett MC, Amidon GL, Gowland PA, Spiller RC, Amidon GE, Marciani L.
11 Stomach Fluid Transport Analysis Simulation in Blue. Clinically Measured Volume using MRI in Red
12 Fluid Transport Analysis of Stomach and Small Intestine Secretion k ss Secretion k si Water Intake 240mL Stomach V S Emptying k qs Intestine V I Exit to Colon Absorption k wa Literature based estimation First order absorption Two Unknowns to Estimate Secretion and Exit to Colon (dependent on transit speed) Minimal
13 Residual Analysis Based on Small Intestine MRT to Develop The Intestinal Fluid Transit Model Surface plot indicates residual (z axis) (blue is low) Overall cumulative exit is similar to MRT in small intestine as previously reported Adv Drug Del Rev Jun 12, 19(3) doi: / X(96) Transport approaches to the biopharmaceutical design of oral drug delivery systems: prediction of intestinal absorption Lawrence X. Yu a, 1, Elke Lipka b, John R. Crison b, Gordon L. Amidon
14 MRI Measurement and Modeling of Small Intestinal Fluid Mol Pharm Sep 2;11(9): doi: /mp500210c. Epub 2014 Aug 19. Quantification of gastrointestinal liquid volumes and distribution following a 240 ml dose of water in the fasted state. Mudie DM 1, Murray K, Hoad CL, Pritchard SE, Garnett MC, Amidon GL, Gowland PA, Spiller RC, Amidon GE, Marciani L. Simulation in Blue. Clinically Measured Volume using MRI in Red
15 MRI Measurement and Modeling of Upper and Lower Small Intestinal Fluid Upper/Lower small intestine fluid volumes were quantified in the MRI study.
16 Clinical Evaluation of Dynamic Fluid Transit Model by GI Intubation and Measurement of Non-absorbable Marker in the GI tract Fasted healthy volunteers Dose 240mL of Phenol Red (Non-absorbable marker) Clinical GI Intubation Study Multi-lumen GI tube 4 aspiration ports to obtain GI samples Multi-Lumen GI Tube
17 Measurement of Phenol Red Concentration in the GI tract and Simulation of Phenol Red Concentration based on Dynamic Volume Change Simulation in Blue. Clinically Measured Phenol Red Concentration in the GI tract in Red More refinement needed
18 Case Study: Apply Dynamic Fluid Transit Model to Predict PK Profile after Oral Dosing of Mesalamine Solution Human volunteers Drug: 125 ml Mesalamine100 mg oral solution, followed by 125 ml water Measure mesalamine plasma concentration for pharmacokinetic parameters analysis Apply dynamic fluid transit model to simulate plasma drug profile Compare with traditional CAT model to simulate plasma drug profile
19 Average plasma concentrations observed for 5-ASA and Ac-5-ASA when administered a dose of 100mg mesalamine solution, 1000mg Pentasa, 1125mg Apriso, or 1200mg Lialda ASA Ac-5-ASA Concentration (nm) Drug Formulation Pentasa Apriso Lialda Solution Time (hr)
20 Individual plasma concentrations observed for 5- ASA (left) and Ac-5-ASA (right) when administered a dose of 100mg mesalamine solution, 1000mg Pentasa, 1125mg Apriso, or 1200mg Lialda. 5-ASA 25 Solution 30 Pentasa Concentration (nm) Apriso Lialda Time (hr)
21 Dynamic Fluid Models Can Better Characterize the Early Absorption Process
22 Dynamic Fluid Transit Model can also be Tuned for the Stomach Volume in Individual Subject Blue: Simulation Red: MRI measurement
23 Dynamic Fluid Transit Model can also be Tuned for the Small Intestine in Individual Subject Blue: Simulation Red: MRI measurement
24 Visualization of Dynamic Fluid Volume Changes and Concentration Gradient in 30 Compartments of GI tract After dosing mesalamine Solution 100mg Model depicts physical transit through GI Left (Duodenum) to Right (Ileum) Three different individuals Low Concentration High Concentration
25 Dynamic Fluid Changes in GI Tract Alter Mesalamine Plasma Profile in Different Individuals Same 100mg solution dosing Same pharmacokinetic parameters Only dynamic volume has changed
26 Summary Dynamic fluid model simulates fluid transit and volume dynamics in stomach and small intestine with 30 compartments, which mimic physiology relevant fluid volumes in human Dynamic fluid model simulates drug concentration in GI tract and in plasma after oral solution dosing Future studies Refine the model to simulate concentration of nonabsorbable marker (Phenol red) in GI tract and validate the model with clinical data (GI concentration in GI tract) Add MMC into current Dynamic fluid model? Simulate drug dissolution in GI tract for Ibuprofen IR formulation and Mesalamine MR formulations (Pentasa, Apriso, Lialda) and validate the model using clinical data (drug concentration in GI tract)
27 Directly Measure In Vivo Drug Dissolution in Human GI tract by Clinical Intubation Study 27
28 In Vivo GI tract Dissolution of Modified Release Formulations and Immediate Release Formulations Modified release formulations of mesalamine in comparison of oral solution Pentasa : 500 mg capsule x 2 Apriso : 375 mg capsule x 3 Lialda : 1200 mg tablet x 1 Mesalamine oral solution: 100 mg/125 ml water, followed by 125 water Immediate release formulations of ibuprofen Fasting State: 800 mg Ibuprofen Fed State: 800 mg of Ibuprofen Phenol red (100 ug/ml) as non absorobable maker 28
29 GI Intubation Tube Design Multi-Lumen GI Tube Multi-lumen GI tube with Tungsten weighted distal tip 4 aspiration channels and 1 channel for guide wire placement Aspiration channels spaced 50 cm apart Manufactured by Arndorfer, Inc., Greendale, Wisconsin Length: 300 cm Diameter: 7 mm Length from mouth to Port 1: 100 cm 29
30 Intubation Procedure in Human GI Tract Port Locations: 1. Distal Jejunum/ Proximal Ileum 2. Proximal Jejunum 3. Duodenum 4. Stomach Fluoroscopic photo of GI tube placement. Shown are 3 aspiration ports located in the stomach, proximal jejunum, and distal jejunum. 30
31 Sample Collection GI fluids Stomach, duodenum, jejunum, early ileum ml at each port at 1, 2, 3, 4, 5, 6, 7 hours Blood 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96 hours Feces 0-12, 12-24, 24-48, 48-72, hours 31
32 5-ASA Ac-5-ASA Average concentrations of 5-ASA and Ac-5-ASA in different regions of small intestine when administered a dose of 1000mg Pentasa, 1125mg Apriso, or 1200mg Lialda 6000 Stomach Duodenum Proximal Jejunum Jejunum Distal Jejunum 4000 Concentration (um) Drug Formulation Pentasa Apriso Lialda Time (hr)
33 5-ASA Ac-5-ASA 5-ASA Ac-5-ASA 5-ASA Ac-5-ASA Pentasa Pentasa Apriso Apriso Lialda Lialda Concentrations of 5-ASA and Ac-5-ASA in different GI regions for each individual subject when administered a dose of 1000mg Pentasa, 1125mg Apriso, or 1200mg Lialda. Concentration (um) Stomach Duodenum Proximal Jejunum Jejunum Distal Jejunum Time (hr)
34 Plasma Ibuprofen Concentration After 800 mg Dose at Fasted and Fed Sates Poster 08W0830 Mark Koenigsknecht Fasted Fed Concentration (ng/ml) Time (hr)
35 Plasma Stomach DuodenumProximal JejunumMid Jejunum Ibuprofen Concentration in Human GI Tract After 800 mg Dose at Fasted and Fed Sates Poster 08W0830 Mark Koenigsknecht Fasted Fed Concentration (ng/ml) 6e+05 4e+05 2e+05 0e+00 6e+05 4e+05 2e+05 0e+00 6e+05 4e+05 2e+05 0e+00 8e+05 6e+05 4e+05 2e+05 0e Time (hr)
36 Acknowledgment UM Clinical Study Team Duxin Sun, Ph.D. Gordon L Amidon, Ph.D. William L. Hasler, M.D. Allen Lee, MD Jason R. Baker, M.S. Hiro Tsume, Ph.D. Ann Frances Fioritto, B.S. Barry Bleske, Pharm.D. Mark Koenigsknecht, Ph.D. Jeff Wysocki, R.N. MICHR nurse team UM Pharmacokinetics Core Alex Yu Bo Wen, Ph.D. Ying Wang, Ph.D. Ruijuan Luo, Ph.D. Siwei Li, Ph.D. Ting Zhao, Ph.D. UM Department of Mathematics Trachette Jackson, PhD Subjects Healthy Volunteers FDA, CDER, OGD Robert Lionberger, Ph.D. Xinyuan (Susie) Zhang, Ph.D. Jeff Jiang, Ph.D. Jianhong Fan, Ph.D. Andrew Babiskin, Ph.D. Thushi Amini, Ph.D. Hong Wen, Ph.D.
37 Duxin Sun Lab Acknowledgment
A Novel Mechanistic and Physiologically-Based Pharmacokinetic Model with Dynamic Gastrointestinal Fluid Transport
A Novel Mechanistic and Physiologically-Based Pharmacokinetic Model with Dynamic Gastrointestinal Fluid Transport by Alex Yu A dissertation submitted in partial fulfillment of the requirements for the
More informationAdvantages and Limitations of In Vivo Predictive Dissolution (IPD) Systems
Advantages and Limitations of In Vivo Predictive Dissolution (IPD) Systems November 16 th Prof. Gregory E. Amidon - University of Michigan What is an In vivo Predictive Dissolution (IPD) System? An IPD
More informationAdvantages and Limitations of In Vivo Predictive Dissolution (IPD) Systems
Advantages and Limitations of In Vivo Predictive Dissolution (IPD) Systems November 16 th Prof. Gregory E. Amidon - University of Michigan What is an In vivo Predictive Dissolution (IPD) System? An IPD
More informationAltered GI absorption in special populations: An industry perspective
Altered GI absorption in special populations: An industry perspective Cordula Stillhart and Neil J. Parrott F. Hoffmann La Roche Ltd, Basel (CH) UNGAP WG meeting, Leuven (B) 8 March 2018 Current challenges
More informationA compartmental absorption and transit model for estimating oral drug absorption
International Journal of Pharmaceutics 186 (1999) 119 125 www.elsevier.com/locate/promis A compartmental absorption and transit model for estimating oral drug absorption Lawrence X. Yu a, *, Gordon L.
More informationUse of PBPK in simulating drug concentrations in pediatric populations: Case studies of Midazolam and Gabapentin
Use of PBPK in simulating drug concentrations in pediatric populations: Case studies of Midazolam and Gabapentin WORKSHOP ON MODELLING IN PAEDIATRIC MEDICINES April 2008 Viera Lukacova, Ph.D. Walter Woltosz,
More informationPQRI Workshop Bethesda 2012
Review of GI physiology and use of biorelevant media PQRI Workshop Bethesda 2012 Prof. Dr. Jennifer Dressman An IVIVC can only be as good as the data used to produce it! With respect to the dissolution
More informationAdvances in Prediction of Food Effects
Advances in Prediction of Food Effects John Crison APS Biopharmaceutics Focus Group MSD Innovation Centre, Hoddesdon, UK June 9, 2011 Outline Introduction/Theory Physiological and Physical Chemical Parameters
More informationMetformin: Mechanistic Absorption Modeling and IVIVC Development
Metformin: Mechanistic Absorption Modeling and IVIVC Development Maziar Kakhi *, Ph.D. FDA Silver Spring, MD 20993 Maziar.kakhi@fda.hhs.gov Viera Lukacova, Ph.D. Simulations Plus Lancaster, CA 93534 viera@simulations-plus.com
More informationDevelopment of Canagliflozin: Mechanistic Absorption Modeling During Late-Stage Formulation and Process Optimization
Development of Canagliflozin: Mechanistic Absorption Modeling During Late-Stage Formulation and Process Optimization Nico Holmstock Scientist, Janssen R&D M CERSI 2017, BALTIMORE (USA) Canagliflozin An
More informationOral Drug Delivery: What to learn from Imaging Studies? An update. Werner Weitschies University of Greifswald
Oral Drug Delivery: What to learn from Imaging Studies? An update Werner Weitschies University of Greifswald werner.weitschies@uni-greifswald.de 8th Global DDF Summit, Berlin, March 28, 2017 Outline Methodologies
More informationPK-UK Challenges and benefits of using PBPK to evaluate an IVIVC for drugs with nonideal solubility and/or permeability. Bath, November 2014
PK-UK 2014 Challenges and benefits of using PBPK to evaluate an IVIVC for drugs with nonideal solubility and/or permeability Bath, November 2014 Prof. Dr. Jennifer Dressman Dressman Bath 2014 Why IVIVC
More information2- Minimum toxic concentration (MTC): The drug concentration needed to just produce a toxic effect.
BIOPHARMACEUTICS Drug Product Performance Parameters: 1- Minimum effective concentration (MEC): The minimum concentration of drug needed at the receptors to produce the desired pharmacologic effect. 2-
More informationGastric, intestinal and colonic absorption of metoprolol in
Br. J. clin. Pharmac. (1985), 19, 85S-89S Gastric, intestinal and colonic absorption of metoprolol in the rat J. DOMENECH', M. ALBA', J. M. MORERA', R. OBACH' & J. M. PLA DELFINA2 'Department of Pharmaceutics,
More informationBiopharmaceutics Lecture-11 & 12. Pharmacokinetics of oral absorption
Biopharmaceutics Lecture-11 & 12 Pharmacokinetics of oral absorption The systemic drug absorption from the gastrointestinal (GI) tract or from any other extravascular site is dependent on 1. 2. 3. In the
More informationThe BCS: Where Do We Go from Here?
The BCS: Where Do We Go from Here? Jennifer Dressman,* James Butler, John Hempenstall, and Christos Reppas Since the Biopharmaceutics Classification System (BCS) was introduced several years ago, it has
More informationUSING PBPK MODELING TO SIMULATE THE DISPOSITION OF CANAGLIFLOZIN
USING PBPK MODELING TO SIMULATE THE DISPOSITION OF CANAGLIFLOZIN Christophe Tistaert PDMS Pharmaceutical Sciences Preformulation & Biopharmaceutics AAPS 2015, FLORIDA (USA) Canagliflozin An orally active
More informationInvestigation of drug absorption from the gastrointestinal tract of man. I. Metoprolol in the stomach, duodenum and jejunum
Br. J. clin. Pharmac. (1985), 19, 97S-15S Investigation of drug absorption from the gastrointestinal tract of man. I. Metoprolol in the stomach, duodenum and jejunum G. JOBIN', A. CORTOT', J. GODBILLON2,
More informationFundamentals of Pharmacology for Veterinary Technicians Chapter 4
(A) (B) Figure 4-1 A, B (C) FIGURE 4-1C The active transport process moves particles against the concentration gradient from a region of low concentration to a region of high concentration. Active transport
More informationSupporting Information Figure S1. Study day diagram. The MRI scans were more frequent for
ASSOCIATED CONTENT Supporting Information. Supporting Information Figure S1. Study day diagram. The MRI scans were more frequent for the first half an hour when gastric emptying was expected to be faster.
More informationBASIC PHARMACOKINETICS
BASIC PHARMACOKINETICS MOHSEN A. HEDAYA CRC Press Taylor & Francis Croup Boca Raton London New York CRC Press is an imprint of the Taylor & Francis Group, an informa business Table of Contents Chapter
More informationph Dependent Drug Delivery System: Review
ph Dependent Drug Delivery System: Review Korake.S.P. SVERI s College of Pharmacy (Poly.), Pandharpur The ph-dependent CTDDS exploit the generally accepted view that ph of the human GIT increases progressively
More informationEnhancement of oral bioavailability of insulin in humans
Neuroendocrinology Letters Volume 30 No. 1 2009 Enhancement of oral bioavailability of insulin in humans Adnan Badwan 1, Mayas Remawi 1, Nidal Qinna 1,4, Amani Elsayed 1,5, Tawfiq Arafat 2, Munther Melhim
More informationExcipient Interactions Relevant For BCS Biowaivers Peter Langguth
Excipient Interactions Relevant For BCS Biowaivers Peter Langguth Department of Pharmaceutical Technology and Biopharmaceutics, Johannes Gutenberg University Mainz, Germany 3rd Symposium on Harmonization
More informationBELLWORK DEFINE: PERISTALSIS CHYME RUGAE Remember the structures of the digestive system 1
BELLWORK DEFINE: PERISTALSIS CHYME RUGAE 2.07 Remember the structures of the digestive system 1 STANDARD 8) Outline basic concepts of normal structure and function of all body systems, and explain how
More informationWhat is Nanotechnology?
Use of Nanotechnology to Optimize Delivery of Probiotics and Prebiotics to Target Sites Ian G Tucker Professor of Pharmaceutical Sciences University of What is Nanotechnology? Some people say they have
More informationGastrointestinal Transit and Drug Absorption
February 2002 Biol. Pharm. Bull. 25(2) 149 164 (2002) 149 Review Gastrointestinal Transit and Drug Absorption Toshikiro KIMURA* and Kazutaka HIGAKI Faculty of Pharmaceutical Sciences, Okayama University,
More informationUSE OF BIO-PREDICTIVE METHODS DURING EARLY FORMULATION SCREENING
USE OF BIO-PREDICTIVE METHODS DURING EARLY FORMULATION SCREENING Jesse L. Kuiper, Ph.D. (Merck) Carrie A. Coutant, Ph.D. (Eli Lilly) Merck Research Laboratories 15-May-2017 1 Acknowledgements 1X Dissolution
More informationPHAR 7633 Chapter 20 Non Compartmental Analysis
Student Objectives for this Chapter PHAR 7633 Chapter 20 Non Compartmental Analysis To understand and use the non compartmental approach to parameter estimation be able to define, use, and calculate the
More informationUsing a technique by which it is possible to study gastro-intestinal absorption
531 J. Physiol. (I956) I34, 53I-537 THE ABSORPTION OF GLUCOSE BY THE INTACT RAT BY P. C. REYNELL AND G. H. SPRAY From the Nuffield Department of Clinical Medicine, University of Oxford (Received 30 May
More informationFeedRite Feeding Tube. Alex Heilman Graham Husband Katherine Jones Ying Lin
FeedRite Feeding Tube Alex Heilman Graham Husband Katherine Jones Ying Lin Problem Statement Gastric bypass is an invasive procedure that requires up to 5 days of hospitalization and has a narrow patient
More informationSimulation of the Nonlinear PK of Gabapentin and Midazolam in. Adult and Pediatric Populations. Population Approach Group in Europe (PAGE)
Simulation of the Nonlinear PK of Gabapentin and Midazolam in Adult and Pediatric Populations Population Approach Group in Europe (PAGE) Meeting June 2006 Brugge, Belgium Walter Woltosz, M.S., M.A.S. Viera
More informationDrug Absorption and Bioavailability
Drug Absorption and Bioavailability Juan J.L. Lertora, M.D., Ph.D. Director Clinical Pharmacology Program October 4, 2012 Office of Clinical Research Training and Medical Education National Institutes
More informationSaliva Versus Plasma Bioequivalence of Rusovastatin in Humans: Validation of Class III Drugs of the Salivary Excretion Classification System
Drugs R D (2015) 15:79 83 DOI 10.1007/s40268-015-0080-1 ORIGINAL RESEARCH ARTICLE Saliva Versus Plasma Bioequivalence of Rusovastatin in Humans: Validation of Class III Drugs of the Salivary Excretion
More informationAug 28 th, 2017 Pierre Daublain
Analyzing the Potential Root Causes of Variability of Pharmacokinetics in Preclinical Species to Inform Derisking Strategies in Discovery and Early Development Aug 28 th, 2017 Pierre Daublain Outline Problem
More informationPHARMACOKINETICS OF DRUG ABSORPTION
Print Close Window Note: Large images and tables on this page may necessitate printing in landscape mode. Applied Biopharmaceutics & Pharmacokinetics > Chapter 7. Pharmacokinetics of Oral Absorption >
More informationDESIGN AND DEVELOPMENT OF COLON TARGETED DRUG DELIVERY SYSTEM OF 5 FLUORURACIL & METRONIDAZOLE
1. Introduction: DESIGN AND DEVELOPMENT OF COLON TARGETED DRUG DELIVERY SYSTEM OF 5 FLUORURACIL & METRONIDAZOLE Oral controlled - release formulations for the small intestine and colon have received considerable
More informationIncludes mouth, pharynx, esophagus, stomach, small intestine, large intestine, rectum, anus. Salivary glands, liver, gallbladder, pancreas
Chapter 14 The Digestive System and Nutrition Digestive System Brings Nutrients Into the Body The digestive system includes Gastrointestinal (GI) tract (hollow tube) Lumen: space within this tube Includes
More informationIn vitro and in vivo deconvolution assessment of drug release kinetics from oxprenolol Oros preparations
Br. J. clin. Pharmac. (1985), 19, 151S-162S In vitro and in vivo deconvolution assessment of drug release kinetics from oxprenolol Oros preparations F. LANGENBUCHER & J. MYSICKA Pharmaceutical Development,
More informationSection Coordinator: Jerome W. Breslin, PhD, Assistant Professor of Physiology, MEB 7208, ,
IDP Biological Systems Gastrointestinal System Section Coordinator: Jerome W. Breslin, PhD, Assistant Professor of Physiology, MEB 7208, 504-568-2669, jbresl@lsuhsc.edu Overall Learning Objectives 1. Characterize
More informationScientific And Regulatory Background For The Revised Bioequivalence Requirements For NTI, Steep Exposure-Response, And Drugs With Complex PK Profiles
Scientific And Regulatory Background For The Revised Bioequivalence Requirements For NTI, Steep Exposure-Response, And Drugs With Complex PK Profiles Liang Zhao, Ph.D. Director, Division of Quantitative
More informationDefine the terms biopharmaceutics and bioavailability.
Pharmaceutics Reading Notes Define the terms biopharmaceutics and bioavailability. Biopharmaceutics: the area of study concerning the relationship between the physical, chemical, and biological sciences
More informationWhat location in the gastrointestinal (GI) tract has tight, or impermeable, junctions between the epithelial cells?
CASE 32 A 17-year-old boy presents to his primary care physician with complaints of diarrhea for the last 2 days. The patient states that he just returned to the United States after visiting relatives
More informationUNIT 5 MAINTENANCE SYSTEMS Digestive System Test Bank
UNIT 5 MAINTENANCE SYSTEMS Digestive System Test Bank Objective 5.01 Describe the basic functions of the digestive system. 1. What is the main function of the digestive system? a. Hold and receive food
More informationCONTROLLED-RELEASE & SUSTAINED-RELEASE DOSAGE FORMS. Pharmaceutical Manufacturing-4
CONTROLLED-RELEASE & SUSTAINED-RELEASE DOSAGE FORMS Pharmaceutical Manufacturing-4 The improvement in drug therapy is a consequence of not only the development of new chemical entities but also the combination
More informationNANO 243/CENG 207 Course Use Only
L6. Drug Administration & Transport by Fluid Motion April 19, 2018 Part I: Drug Administration Routes of Drug Administration Topical: local effect, substance is applied directly where its action is desired.
More informationDigestive System 7/15/2015. Outline Digestive System. Digestive System
Digestive System Biology 105 Lecture 18 Chapter 15 Outline Digestive System I. Functions II. Layers of the GI tract III. Major parts: mouth, pharynx, esophagus, stomach, small intestine, large intestine,
More informationPredictive modeling of deposition, dissolution, absorption and systemic exposure
Predictive modeling of deposition, dissolution, absorption and systemic exposure IPAC-RS/UF Orlando Inhalation Conference March 20, 2014 Per Bäckman and Bo Olsson, AstraZeneca R&D, Mölndal Sweden The views
More informationMechanistic Transport Analysis to Predict In Vivo Oral Bioperformance. Deanna M. Mudie
Mechanistic Transport Analysis to Predict In Vivo Oral Bioperformance by Deanna M. Mudie A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Pharmaceutical
More informationChapter 2 Rationale and Objective
Chapter 2 SPP School of Pharmacy & Technology Management, SVKM s NMIMS, Mumbai 44 2.0 Rationale Need for extended release drug delivery systems Over the past 50 years or so, substantial research in the
More informationLecture 1: Physicochemical Properties of Drugs and Drug Disposition
Lecture 1: Physicochemical Properties of Drugs and Drug Disposition Key objectives: 1. Be able to explain the benefits of oral versus IV drug administration 2. Be able to explain the factors involved in
More informationPharmacokinetic Modeling & Simulation in Discovery and non-clinical Development
Pharmacokinetic Modeling & Simulation in Discovery and non-clinical Development Where do we stand? Disclaimer I am not a bioinformatician, mathematician or biomedical engineer. I am a simple minded pharmacist,
More informationRevised European Guideline on PK and Clinical Evaluation of Modified Release Dosage Forms
1st MENA Regulatory Conference on Bioequivalence, Biowaivers, Bioanalysis and Dissolution Jordan September 23 24, 2013 Revised European Guideline on PK and Clinical Evaluation of Modified Release Dosage
More informationNUTRIENT DIGESTION & ABSORPTION
NUTRIENT DIGESTION & ABSORPTION NUTR 2050: Nutrition for Nursing Professionals Mrs. Deborah A. Hutcheon, MS, RD, LD Lesson Objectives At the end of the lesson, the student will be able to: 1. Differentiate
More informationBiopharmaceutics Drug Disposition Classification System (BDDCS) --- Its Impact and Application
Biopharmaceutics Drug Disposition Classification System (BDDCS) --- Its Impact and Application Leslie Z. Benet, Ph.D. Professor of Bioengineering and Therapeutic Sciences Schools of Pharmacy and Medicine
More informationBioequivalence of Oral Generic Product with An Alternate Administration
Bioequivalence of Oral Generic Product with An Alternate Administration Minglei Cui, Ph.D. CDR, U.S. Public Health Service Division of Bioequivalence 2 Office of Generic Drugs CDER/FDA 1 Disclaimer & Disclosure
More informationDigestive System. Digestive System. Digestion is the process of reducing food to small molecules that can be absorbed into the body.
Digestive System Digestion is the process of reducing food to small molecules that can be absorbed into the body. 2 Types of Digestion Mechanical digestion physical breakdown of food into small particles
More informationThe digestive tract of the pig
The digestive tract of the pig 2010-11-26 J.P. Rowan1, K.L. Durrance2, G.E. Combs3 and L.Z. Fisher4 1Extension Agent - Agriculture, 4-h, Suwannee County 2professor, Animal Science Department 3professor,
More informationJack Cook, PhD & Vivek Purohit, PhD Clinical Pharmacology Pfizer, Inc.
Challenges and Strategies to Facilitate Formulation Development of Pediatric Drug Products Biopharmaceutical Considerations in Pediatric Formulation Development Jack Cook, PhD & Vivek Purohit, PhD Clinical
More informationA model for cholesterol absorption: isotope vs. mass; single dose vs. constant infusion
A model for cholesterol absorption: isotope vs. mass; single dose vs. constant infusion Donald B. Zilversmit' Division of Nutritional Sciences and Section of Biochemistry, Molecular and Cell Biology, Division
More informationStrategies for Developing and Validating PBPK Models for Extrapolation to Unstudied Population
Strategies for Developing and Validating PBPK Models for Extrapolation to Unstudied Population Nina Isoherranen Department of Pharmaceutics University of Washington Processes driving drug disposition are
More informationViera Lukacova Director, Simulation Sciences
Use of In Silico Mechanistic Models to Support Interspecies Extrapolation of Oral Bioavailability and Formulation Optimization: Model Example Using GastroPlus Viera Lukacova Director, Simulation Sciences
More informationHome Total Parenteral Nutrition for Adults
Home Total Parenteral Nutrition for Adults Policy Number: Original Effective Date: MM.08.007 05/21/1999 Line(s) of Business: Current Effective Date: PPO, HMO, QUEST Integration 05/27/2016 Section: Home
More informationDrug Absorption and Bioavailability
Drug Absorption and Bioavailability Juan J.L. Lertora, M.D., Ph.D. Director Clinical Pharmacology Program October 1, 2015 Office of Clinical Research Training and Medical Education National Institutes
More informationDrug Absorption and Bioavailability
Drug Absorption and Bioavailability Juan J.L. Lertora, M.D., Ph.D. Director Clinical Pharmacology Program October 1, 2015 Office of Clinical Research Training and Medical Education National Institutes
More information* Produces various chemicals to break. down the food. * Filters out harmful substances * Gets rid of solid wastes
* * Produces various chemicals to break down the food * Filters out harmful substances * Gets rid of solid wastes * *Mouth *Pharynx *Oesophagus *Stomach *Small and large intestines * *Changes the physical
More informationDigestive System. How your body obtains nutrients. Wednesday, March 2, 16
Digestive System How your body obtains nutrients Vocabulary Ingestion: food enters the system Physical and enzymatic breakdown begins Digestion: Further breakdown Chemical/enzymatic Vocabulary Absorption:
More informationIntroduction to. Pharmacokinetics. University of Hawai i Hilo Pre-Nursing Program NURS 203 General Pharmacology Danita Narciso Pharm D
Introduction to 1 Pharmacokinetics University of Hawai i Hilo Pre-Nursing Program NURS 203 General Pharmacology Danita Narciso Pharm D 2 Learning objectives Understand compartment models and how they effects
More informationProtein Content (grams) 25 g 5 g 30 g 0 g 28 g 2 g. 20 g 10 g 30 g 0 g 27 g 3 g. 20 g 10 g 20 g 10 g 26 g 4 g. 10 g 20 g 10 g 20 g 10 g 20 g
Digestive Enzymes Introduction: A person is eating a food item. The food contains 30 grams of starch (a polysaccharide), 30 grams of protein and 30 grams of triglycerides (a lipid). Samples of digestive
More informationPhysiologically relevant in vitro methodology to determine true digestibility of carbohydrates and to predict the glycaemic response
Physiologically relevant in vitro methodology to determine true digestibility of carbohydrates and to predict the glycaemic response TNO Quality of Life, Zeist, The Netherlands TIM-Carbo Robert Havenaar
More informationANATOMY & PHYSIOLOGY ONLINE COURSE - SESSION 13 THE DIGESTIVE SYSTEM
ANATOMY & PHYSIOLOGY ONLINE COURSE - SESSION 13 THE DIGESTIVE SYSTEM The digestive system also known as the alimentary canal or gastrointestinal tract consists of a series of hollow organs joined in a
More informationPrinciples of Toxicokinetics/Toxicodynanics
Biochemical and Molecular Toxicology ENVR 442; TOXC 442; BIOC 442 Principles of Toxicokinetics/Toxicodynanics Kim L.R. Brouwer, PharmD, PhD kbrouwer@unc.edu; 919-962-7030 Pharmacokinetics/ Toxicokinetics:
More informationTHE DIGESTIVE SYSTEM THE FOUR STEPS OF DIGESTION
THE DIGESTIVE SYSTEM WHAT IS THE DIGESTIVE SYSTEM? the digestive system is a long, muscular tube The entire system is approximately 9m in length and is usually a one way tract WHY DO WE NEED A DIGESTIVE
More informationBioequivalence (BE), 505(b)(2), Safety and Efficacy Consideration for Injectable Complex Formulations
Bioequivalence (BE), 505(b)(2), Safety and Efficacy Consideration for Injectable Complex Formulations Duxin Sun, Ph.D. J.G. Searle Endowed Professor Director of Pharmacokinetics Core Department of Pharmaceutical
More informationMagnetic Resonance Imaging Quantification of Fasted State Colonic Liquid Pockets in Healthy Humans
This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. pubs.acs.org/molecularpharmaceutics
More informationAn integrated glucose homeostasis model of glucose, insulin, C-peptide, GLP-1, GIP and glucagon in healthy subjects and patients with type 2 diabetes
An integrated glucose homeostasis model of glucose, insulin, C-peptide, GLP-1, GIP and glucagon in healthy subjects and patients with type 2 diabetes Oskar Alskär, Jonatan Bagger, Rikke Røge, Kanji Komatsu,
More informationEffect of Common Excipients on the Oral Drug Absorption of Biopharmaceutics Classification System Class 3 Drugs
Effect of Common Excipients on the Oral Drug Absorption of Biopharmaceutics Classification System Class 3 Drugs James E. Polli jpolli@rx.umaryland.edu April 26, 2016 Topics BCS Class 3 excipient study
More informationEarly BioPharm Risk Assessment in Discovery. Linette Ruston PCF9 17 th September 2010, Barcelona
Early BioPharm Risk Assessment in Discovery Linette Ruston PCF9 17 th September 2010, Barcelona Outline Background Why? How? cmad and early absorption simulation Case Studies & Examples Summary 2 Poor
More informationMedications and ostomies. Sarah Drost, BSc Pharm, RPh, ACPR
Medications and ostomies Sarah Drost, BSc Pharm, RPh, ACPR Overview 1. Medication absorption 2. Medication forms 1. Oral medications 2. Non-oral medication routes 3. Monitoring medications 4. Specific
More informationConferencia Inaugural
Conferencia Inaugural UNDERSTANDING GASTRIC DIGESTION TO DEVELOP NEW FOODS FOR HEALTH R. Paul Singh Distinguished Professor of Food Engineering Department of Biological and Agricultural Engineering University
More informationChapter 22 The Digestive System. Yoon Seo Orite, Jack Kohm, And Jackson Masuda
Chapter 22 The Digestive System Yoon Seo Orite, Jack Kohm, And Jackson Masuda Main Idea The digestive system breaks down ingested food and provides necessary nutrients to the body through various processes.
More informationDIGESTIVE SYSTEM CLASS NOTES. tube along with several
DIGESTIVE SYSTEM CLASS NOTES Digestion Breakdown of food and the of nutrients in the bloodstream. Metabolism Production of for and cellular activities. The digestive system is composed of the canal which
More informationChapter 20 The Digestive System Exam Study Questions
Chapter 20 The Digestive System Exam Study Questions 20.1 Overview of GI Processes 1. Describe the functions of digestive system. 2. List and define the four GI Processes: 20.2 Functional Anatomy of the
More informationPharmacokinetics of ibuprofen in man. I. Free and total
Pharmacokinetics of ibuprofen in man. I. Free and total area/dose relationships Ibuprofen kinetics were studied in 15 subjects after four oral doses. Plasma levels of both total and free ibuprofen were
More informationACETYLSALICYLIC ACID AND IONIC FLUXES ACROSS THE GASTRIC MUCOSA OF MAN
GASTROENTEROLOGY Copyright 1968 by The Williams & Wilkins Co. Vol. 54, No.4, Part 1 of 2 Parts Printed in U.S.A. ACETYLSALICYLIC ACID AND IONIC FLUXES ACROSS THE GASTRIC MUCOSA OF MAN BERGEIN F. OVERHOLT,
More informationA. Incorrect! The esophagus connects the pharynx and the stomach.
Human Physiology - Problem Drill 19: Digestive Physiology and Nutrition Question No. 1 of 10 Instructions: (1) Read the problem and answer choices carefully, (2) Work the problems on paper as 1. This organ
More informationHuman Obestatin ELISA
K-ASSAY Human Obestatin ELISA For the quantitative determination of obestatin in human serum and plasma Cat. No. KT-495 For Research Use Only. 1 Rev. 081309 K-ASSAY PRODUCT INFORMATION Human Obestatin
More informationSmall-Bowel and colon Transit. Mahsa Sh.Nezami October 2016
Small-Bowel and colon Transit Mahsa Sh.Nezami October 2016 Dyspeptic symptoms related to dysmotility originating from the small bowel or colon usually include : Abdominal pain Diarrhea Constipation However,
More informationRebel Biology - Nutrition. organisms need a variety of nutrients to perform life s activities. carbs, proteins. vitamins, water,
Rebel Biology - Nutrition organisms need a variety of nutrients to perform life s activities the most important ones are fats, carbs, proteins vitamins, water, these either provide direct value(fats/carbs/proteins)
More informationLong-Term Care Updates
Long-Term Care Updates May 2016 By Katee Miller, PharmD Candidate, Mohamed Jalloh, PharmD, & Zara Risoldi Cochrane, PharmD, MS, FASCP Introduction Enteral nutrition (EN) through a tube is the preferred
More informationThe Digestive System. Prepares food for use by all body cells.
The Digestive System Prepares food for use by all body cells. Digestion The chemical breakdown of complex biological molecules into their component parts. Lipids to fatty acids Proteins to individual amino
More informationHuman Body Drug Distribution
Human Body Drug Distribution Nathan Liles Benjamin Munda Directed by Dr. Miguel Bagajewicz TABLE OF CONTENTS Table of Figures... 3 Executive Summary... 4 Introduction... 5 Background... 5 Theory... 6 Absorption...
More informationBiopharmaceutics Dosage form factors influencing bioavailability Lec:5
Biopharmaceutics Dosage form factors influencing bioavailability Lec:5 Ali Y Ali BSc Pharmacy MSc Industrial Pharmaceutical Sciences Dept. of Pharmaceutics School of Pharmacy University of Sulaimani 09/01/2019
More informationNURSE-UP DIGESTIVE SYSTEM AKA G.I. SYSTEM
NURSE-UP DIGESTIVE SYSTEM AKA G.I. SYSTEM The digestive system is used for breaking down food into nutrients which then pass into the circulatory system and are taken to where they are needed in the body.
More informationBCS: Dissolution Testing as a Surrogate for BE Studies
BCS: Dissolution Testing as a Surrogate for BE Studies Dirk M Barends National Institute of Public Health and the Environment The Netherlands APV / IKEV Seminar on Bioavailability and Bioequivalence, Istanbul,
More informationThe use of Saliva instead of Plasma as a Surrogate in Drug Bioavailability and Bioequivalence Studies in Humans
The use of Saliva instead of Plasma as a Surrogate in Drug Bioavailability and Bioequivalence Studies in Humans ا.د. ناصر محمد ياسر نمرادكيدك Prof. Nasir M. Idkaidek University of Petra Amman - Jordan
More information2. A digestive organ that is not part of the alimentary canal is the: a. stomach b. liver c. small intestine d. large intestine e.
Chapter 14 The Digestive System and Body Metabolism Review Questions Multiple Choice: 1. Which of the following terms are synonyms? a. Gastrointestinal tract b. Digestive system c. Digestive tract d. Alimentary
More informationGoals. The Hindgut 4/10/2014. Equine Digestive Tract. Week 2 Lecture 4
Equine Digestive Tract Week 2 Lecture 4 Clair Thunes, PhD Animal Science 126 Equine Nutrition Goals Know the main anatomical sections of the hindgut, their functions and purpose Sites of potential impactions
More information