Basic pharmacokinetics. Frédérique Servin APHP hôpital Bichat Paris, FRANCE

Size: px
Start display at page:

Download "Basic pharmacokinetics. Frédérique Servin APHP hôpital Bichat Paris, FRANCE"

Transcription

1 Basic pharmacokinetics Frédérique Servin APHP hôpital Bichat Paris, FRANCE

2 DOSE CONCENTRATION EFFECT Pharmacokinetics What the body does to the drug Pharmacodynamics What the drug does to the body Transfer to the effect site: PK or PD? Estimation of the transfer to the effect site requires a measure of effect

3 Pharmacokinetic steps Absorption Digestive Trans-mucosal (nasal; sub-lingual; rectal ) Distribution Elimination / transformation Metabolism Excretion in bile or urine

4 Absorption: first pass effect

5 Distribution Describes the diffusion (active or passive) of a drug in various tissues. The penetration of the drug varies with different tissues. If the drug is protein bound, only the free (active) fraction will be distributed Acid drugs are bound to plasma albumin Basic drugs are bound to a1-acid-glycoprotein BUT if the affinity for the metabolic enzyme is superior to that for the binding protein, the binding will not limit the clearance (non restrictive clearance)

6 Protein binding of anaesthetic agents Albumin a1 AGP binding <50% Thiopental Fentanyl Ketamine Propofol Alfentanil Pancuronium Etomidate Sufentanil Vecuronium Midazolam Remifentanil Rocuronium Flumazenil Atracurium Morphine Cisatracurium

7 Hepatic drug elimination The liver renders xenobiotics accessible to excretion in urine or bile water-soluble Biliary excretion Metabolism Phase 1 reactions Hydrolysis Oxidation (CYP 450) Reduction Phase 2 reactions Conjugation +++ Methylation, acetylation.

8 Hepatic clearance Cl H = Q H E = Q H [ [Cl i ] / [Q H + Cl i ] ] If E is close to 1, Cl H ~ Q H The clearance is flow rate dependant If E is small (low extraction), Cl i is small compared to Q H, thus [Cl i ] / [Q H + Cl i ] is close to Cl i / Q H, and Cl H ~ Q H [Cl i / Q H ] ~ Cl i The clearance is enzyme dependent, and insensitive to changes in blood flow

9 Hepatic clearance of anaesthetic agents Rate dependant Intermediate Enzyme dependant Propofol Midazolam Thiopental Etomidate Alfentanil Diazepam Ketamine Vecuronium Lorazepam Flumazenil Bupivacaïne Flunitrazepam Morphine Fentanyl Sufentanil lidocaïne

10 Hepatic metabolism of anaesthetic agents Phase 1 CP450 Phase 1 other Phase 2 Thiopental Etomidate Propofol Ketamine (Atracurium) Morphine Midazolam Flumazenil Fentanyl Sufentanil Alfentanil (Vecuronium) (Rocuronium)

11 Application of pharmacokinetics to clinical anaesthesia

12 Concentration (µg/ml) Pharmacokinetic analysis C1 = A * e -a*t C2 = B * e -b*t C3 = C * e -g*t Time (min) This three exponential analysis can be modified (MATHS!!!) in other forms «compartment analysis»

13 Pharmacokinetic model V2 CL2 V1 CL3 V3 1 - V1, V2, V3, Cl1, Cl2, Cl3 2 V1, k10, k12, k21, k13, k31 CL1 Cl1 = V1*k10 Cl2 = V1*k12 = V2*k21 V2 = V1* (k12/k21)

14 Compartmental models Simple ++ (max 3 cpts) Actually not much to do with reality the drug concentration drug is assumed to be uniformly equal within the compartment, with instant homogeneous distribution Mammillary model (the peripheral compartments are only connected through the central one) Elimination usually occurs only from the central compartment Advantage: they work! At least at the level of complexity adequate for clinical practice

15 conc Bring the drug concentration in the «therapeutic» zone and keep it there as long as necessary time (min)

16 The BET Bolus The target concentration is obtained by filling up the central compartment Elimination A constant rate infusion Compensates metabolism and / or excretion Transfer A gradually decreasing rate infusion Compensates the distribution to the peripheral compartments V2 V3 V1 CL2 CL3 CL1 Lauven et al A microprocessor controlled infusion scheme for midazolam to achieve constant plasma levels, Anaesthesist 31: 15-20, 1982)

17 BET equations Bolus: Elimination: Ct X V1 Transfer... Ct X Cl = Ct X V1 X k 10 Ct X V1(k 12 e (-k 21 t) + k 13 e (-k 31 t) ) Maintenance rate infusion is therefore: Dose = Ct X V1 (k 10 +k 12 e (-k 21 t) + k 13 e (-k 31 t) )

18 Building a PK model Patients or healthy volunteers Bolus dose or infusion Many blood samples (critical phases) Two stages analysis Population kinetics

19 Population kinetics Blood samples from all the patients are studied together (pooled approach) Significant covariates improve the statistical likelihood of the model (ex : weight, age, sex ) The influence of the covariates is considered for every parameter. Bayesian adaptation allows the estimation of individual parameters (posthoc values) Some populations (children) require specific models

20 Induction

21 Effect site concentration, fentanyl Scott, Anesthesiology 1985

22 Time course of action : alfentanil Scott J, Anesthesiology, 1985

23 Hysteresis d effet effet conc

24 Cl1 = V1 x k10 Cl2 = V1 x k12 = V2 x k21 Cl4 = V1 x k14 = VE x ke0; VE = e, so k14 = e, and V1 is proportional to Ke0 V2 V1 V3 CL2 CL3 ke 0 CL1 Effect site

25 Time to peak effect is a physiological variable independent from the model The ke0 constant associated to the pharmacokinetic model is dependent on the PK model and the time to peak effect Female, 75 y.o., 62 kg, 59 cm propofol 70 mg, no opioid BIS Time to peak = 2.2 min Marsh model V1 = 14.1 L Ke0 = 1.11 (0.267) Schnider s model V1 = 4.27 L Ke0 = (0.456)

26 % of EEG maximum effect Opioids time to peak effect. 100 sufentanil fentanyl 40 alfentanil 20 0 remifentanil Minto et al, Anesthesiology 1997

27 Onset time time to peak effect Conc (ng/ml) Minimum concentration recommanded with remifentanil (3 ng/ml) time (min) Alfentanil Rémifentanil Sufentanil Fentanyl Lower concentration limit for endotracheal intubation

28 Effect site concentration, therapeutic window Propofol bolus, 2.5 mg/kg Propofol conc ( µ g/ml) 12 plasma Effect site time (min)

29 Instantaneous mixing is an approximation Avram, Anesthesiology 2003

30 Pharmacokinetic models currently used for propofol TCI Marsh (1991) V1 = 0.228*TBW K10 = min -1 K12 = min -1 K13 = min -1 K21 = min -1 K31 = min -1 Ke0 Diprifusor Ke0 Base Primea 1.21 Azena PK Tpeak 1.6min Schnider (1998) V1 = 4.27 L V2 = *(age-53) L V3 = 238 L Cl1 = *(TBW-77) *(LBM-59) *(height-177) L/min -1 Cl2 = *(age 53) L/min -1 Cl3 = L/min -1 Ke0 = 0.456

31 Maintenance

32 Concentration / effect relationship probability of effect E EmaxC y EC50 g Cg efficiency range 10 0 EC95 EC concentration

33 Hypnotics Opioids Stimuli

34 Recovery

35 From maintenance to recovery Vuyk, Anesthesiology 1997

36 Alfentanil Vuyk, Anesthesiology Dec. 1997

37 Remifentanil Vuyk, Anesthesiology Dec. 1997

38 7 6 Propofol conc. (µg/ml) 5 4 Context sensitive half life 3 2 Decrement time 1 0 time (min)

39 The recovery time depends on the ratio between the maintenance concentration and the C50 for recovery 6 5 End of infusion Time (min)

40 Context Sensitive Half Time Shafer SL, ASA Refresher Course, Chapter 19, 1996

41 Are drug models predictive? Mathematical models of drug behaviour incorporating effect site concentrations and drug interactions predict anaesthetic drug effect (e.g., loss of response to stimulation) as well as: Measured concentrations BIS AAI I am not aware of any counter examples. Slide S. Shafer

42 Remember Thinking in concentration is mandatory to understand a drug time course of effect and interactions Mathematics are necessary to predict drug concentration over time (thus effect) BUT pharmacokinetics is primarily proteins, enzymes, liver, kidney, blood, fluids and cells! If you understand pharmacokinetics, you will be able to understand what happens to your drug even in patients widely different from the standard population

Principles of Pharmacokinetics

Principles of Pharmacokinetics Principles of Pharmacokinetics Ákos Csomós MD, PhD Associate Professor Institute of Anaesthesia and Critical Care, Semmelweis University, Budapest, Hungary Pharmacokinetics: Very basics How the organ affects

More information

Pharmacokinetics of drug infusions

Pharmacokinetics of drug infusions SA Hill MA PhD FRCA Key points The i.v. route provides the most predictable plasma concentrations. Pharmacodynamic effects of a drug are related to plasma concentration. Both plasma and effect compartments

More information

Pharmacology in the obese : does weight matter?

Pharmacology in the obese : does weight matter? A A Pharmacology in the obese : does weight matter? Michel MRF Struys, MD, PhD Professor and Chair, Department of Anesthesia University Medical Center Groningen Groningen, The Netherlands Professor of

More information

Richard A. Beers, M.D. Professor, Anesthesiology SUNY Upstate Medical Univ VA Medical Center Syracuse, NY

Richard A. Beers, M.D. Professor, Anesthesiology SUNY Upstate Medical Univ VA Medical Center Syracuse, NY Richard A. Beers, M.D. Professor, Anesthesiology SUNY Upstate Medical Univ VA Medical Center Syracuse, NY beersr@verizon.net 2 Improvements in safety and advances in care are re-invested in older, sicker

More information

Sign up to receive ATOTW weekly Regarding the use of propofol in total intravenous anaesthesia:

Sign up to receive ATOTW weekly Regarding the use of propofol in total intravenous anaesthesia: TARGET CONTROLLED INFUSIONS IN ANAESTHETIC PRACTICE ANAESTHESIA TUTORIAL OF THE WEEK 75 26th NOVEMBER 2007 Dr Subash Sivasubramaniam University Hospitals of North Staffordshire subashken@yahoo.com SELF

More information

Time to Lowest BIS after an Intravenous Bolus and an Adaptation of the Time-topeak-effect

Time to Lowest BIS after an Intravenous Bolus and an Adaptation of the Time-topeak-effect Adjustment of k e0 to Reflect True Time Course of Drug Effect by Using Observed Time to Lowest BIS after an Intravenous Bolus and an Adaptation of the Time-topeak-effect Algorithm Reported by Shafer and

More information

Pharmacology of intravenous induction agents. Frederique S Servin APHP - Hôpital Bichat Paris FRANCE

Pharmacology of intravenous induction agents. Frederique S Servin APHP - Hôpital Bichat Paris FRANCE Pharmacology of intravenous induction agents Frederique S Servin APHP - Hôpital Bichat Paris FRANCE Intravenous induction agents currently available thiopental propofol etomidate midazolam ketamine Common

More information

EUROANESTHESIA 2006 BASIC PHARMACOKINETICS FOR THE CLINICIAN INTRODUCTION BASIC PARAMETERS COMPARTMENTAL MODELS. Madrid, Spain, 3-6 June RC2

EUROANESTHESIA 2006 BASIC PHARMACOKINETICS FOR THE CLINICIAN INTRODUCTION BASIC PARAMETERS COMPARTMENTAL MODELS. Madrid, Spain, 3-6 June RC2 BASIC PHARMACOKINETICS FOR THE CLINICIAN EUROANESTHESIA 2006 Madrid, Spain, 3-6 June 2006 9RC2 THOMAS W. SCHNIDER Institute for Anesthesiology Kantonsspital St.Gallen, Switzerland CHARLES F. MINTO Department

More information

Cover Page. The handle holds various files of this Leiden University dissertation.

Cover Page. The handle   holds various files of this Leiden University dissertation. Cover Page The handle http://hdl.handle.net/1887/2959 holds various files of this Leiden University dissertation. Author: Diepstraten, Jeroen Title: The influence of morbid obesity on the pharmacokinetics

More information

Pharmacokinetic models for propofol defining and illuminating the devil in the detail

Pharmacokinetic models for propofol defining and illuminating the devil in the detail British Journal of Anaesthesia 13 (1): 26 37 (29) doi:1.193/bja/aep143 Advance Access publication June 1, 29 Pharmacokinetic models for propofol defining and illuminating the devil in the detail A. R.

More information

Chapter 25. General Anesthetics

Chapter 25. General Anesthetics Chapter 25 1. Introduction General anesthetics: 1. Analgesia 2. Amnesia 3. Loss of consciousness 4. Inhibition of sensory and autonomic reflexes 5. Skeletal muscle relaxation An ideal anesthetic: 1. A

More information

Applications for Anaesthesia. arcomed syringe and infusion pumps

Applications for Anaesthesia. arcomed syringe and infusion pumps Applications for Anaesthesia arcomed syringe and infusion pumps TIVA TCI PCA PCEA PCS PIEB Anaesthesia programs and applications for arcomed Infusion Devices TIVA TCI PCA PCEA PCS PIEB (Total Intravenous

More information

Basic Pharmacokinetic Principles Stephen P. Roush, Pharm.D. Clinical Coordinator, Department of Pharmacy

Basic Pharmacokinetic Principles Stephen P. Roush, Pharm.D. Clinical Coordinator, Department of Pharmacy Basic Pharmacokinetic Principles Stephen P. Roush, Pharm.D. Clinical Coordinator, Department of Pharmacy I. General principles Applied pharmacokinetics - the process of using drug concentrations, pharmaco-kinetic

More information

Total. Intravenous. ANAESTHESIA using target contro. Elderly. MAC Critica ill. Obese. Col Acad. College of Anaesthesiologists,

Total. Intravenous. ANAESTHESIA using target contro. Elderly. MAC Critica ill. Obese. Col Acad. College of Anaesthesiologists, Total Intravenous ANAESTHESIA using target contro controlled infusion A pocket p reference Elderly MAC Critically Critica ill O Obese College of Anaesthesiologists, Col Acad Academy of Medicine of Malaysia

More information

ASSESSMENT OF THE PAEDIATRIC NEEDS ANAESTHESIOLOGY DISCLAIMER

ASSESSMENT OF THE PAEDIATRIC NEEDS ANAESTHESIOLOGY DISCLAIMER European Medicines Agency Evaluation of Medicines for Human Use ASSESSMENT OF THE PAEDIATRIC NEEDS ANAESTHESIOLOGY London, October 2006 Doc. Ref: EMEA/405166/2006 DISCLAIMER The Paediatric Working Party

More information

BIOPHARMACEUTICS and CLINICAL PHARMACY

BIOPHARMACEUTICS and CLINICAL PHARMACY 11 years papers covered BIOPHARMACEUTICS and CLINICAL PHARMACY IV B.Pharm II Semester, Andhra University Topics: Absorption Distribution Protein binding Metabolism Excretion Bioavailability Drug Interactions

More information

Pharmacokinetics in the critically ill. Intensive Care Training Program Radboud University Medical Centre Nijmegen

Pharmacokinetics in the critically ill. Intensive Care Training Program Radboud University Medical Centre Nijmegen Pharmacokinetics in the critically ill Intensive Care Training Program Radboud University Medical Centre Nijmegen In general... Critically ill patients are at higher risk for ADE s and more severe ADE

More information

Pharmacokinetics One- compartment Open Model Lec:2

Pharmacokinetics One- compartment Open Model Lec:2 22 Pharmacokinetics One- compartment Open Model Lec:2 Ali Y Ali BSc Pharmacy MSc Industrial Pharmaceutical Sciences Dept. of Pharmaceutics School of Pharmacy University of Sulaimani 1 Outline Introduction

More information

Optimization Methods to Minimize Emergence Time While Maintaining Adequate Post-Operative Analgesia

Optimization Methods to Minimize Emergence Time While Maintaining Adequate Post-Operative Analgesia Optimization Methods to Minimize Emergence Time While Maintaining Adequate ost-operative Analgesia arl Tams BS, Noah Syroid MS, Ken B. Johnson MD, Talmage D. Egan MD, Dwayne Westenskow hd ABSTAT A rapid

More information

PART 1. Pharmacology

PART 1. Pharmacology PART 1 Pharmacology WEB_01.indd 1 7/5/2006 10:10:33 AM WEB_01.indd 2 7/5/2006 10:10:33 AM CHAPTER 1 Pharmacokinetic principles Michel M.R.F. Struys, Alain Kalmar and Peter De Paepe Introduction Pharmacokinetics

More information

SEDATION FOR SMALL PROCEDURES

SEDATION FOR SMALL PROCEDURES SEDATION FOR SMALL PROCEDURES Sinno Simons Erasmus MC Sophia Children s Hospital Rotterdam, the Netherlands s.simons@erasmusmc.nl SEDATION in newborns How and when How to evaluate How to dose Why to use

More information

REVIEW Pharmacokinetic-pharmacodynamic relationship of anesthetic drugs: from modeling to clinical use [version 1; referees: 4 approved]

REVIEW Pharmacokinetic-pharmacodynamic relationship of anesthetic drugs: from modeling to clinical use [version 1; referees: 4 approved] REVIEW Pharmacokinetic-pharmacodynamic relationship of anesthetic drugs: from modeling to clinical use [version 1; referees: 4 approved] Valerie Billard Department of Anesthesia and surgical intensive

More information

PHA5128 Dose Optimization II Case Study I Spring 2013

PHA5128 Dose Optimization II Case Study I Spring 2013 Silsamicin is an investigational compound being evaluated for its antimicrobial effect. The route of administration for this drug is via intravenous bolus. Approximately 99.9% of this drug is eliminated

More information

Analgesia is a labeled indication for all of the approved drugs I will be discussing.

Analgesia is a labeled indication for all of the approved drugs I will be discussing. Comparative Opioid Pharmacology Disclosure Analgesia is a labeled indication for all of the approved drugs I will be discussing. I ve consulted with Glaxo (remifentanil), Abbott (remifentanil), Janssen

More information

Cover Page. The handle holds various files of this Leiden University dissertation.

Cover Page. The handle   holds various files of this Leiden University dissertation. Cover Page The handle http://hdl.handle.net/1887/20616 holds various files of this Leiden University dissertation. Author: Lichtenbelt, Bart Jan Title: PK-PD modelling of the interaction of propofol and

More information

Pharmacokinetic concepts for TCI anaesthesia

Pharmacokinetic concepts for TCI anaesthesia Pharmacokinetic concepts for TCI anaesthesia E. Gepts Department of Anaesthesiology, UVC Sint Pieter, 322 Hoogstraat, 1000 Brussels, Belgium Summary The development of new short-acting anaesthetic drugs,

More information

!Intra-Operative Reactions!

!Intra-Operative Reactions! XXII World Allergy Congress Drug Allergy: Management of Drug Hypersensitivity!!Intra-Operative Reactions! Prof Pascal DEMOLY! Division of Allergy! University Hospital of Montpellier! INSERM U657! France!

More information

MR04A3 An isoindoline derivative, New Sedative/Anesthetic Agent

MR04A3 An isoindoline derivative, New Sedative/Anesthetic Agent MR04A3 An isoindoline derivative, ew Sedative/Anesthetic Agent ovember 2009 1 Introduction Sedatives are widely used in: Settings providing stressful and painful procedures Gastroenterology (colonoscopy

More information

Original Date of issue: 01/11/2005 Last Reviewed: 01/05/2011 Version:4 Page 1 of 7

Original Date of issue: 01/11/2005 Last Reviewed: 01/05/2011 Version:4 Page 1 of 7 Original Date of issue: 01/11/2005 Last eviewed: 01/05/2011 Version:4 Page 1 of 7 15: Anaesthesia 15.1 General anaesthesia 15.1.1 Intravenous anaesthesia Etomidate Injection (20mg/10ml) Ketamine Injection

More information

It the process by which a drug reversibly leaves blood and enter interstitium (extracellular fluid) and/ or cells of tissues.

It the process by which a drug reversibly leaves blood and enter interstitium (extracellular fluid) and/ or cells of tissues. It the process by which a drug reversibly leaves blood and enter interstitium (extracellular fluid) and/ or cells of tissues. Primarily depends on: 1.Regional blood flow. 2.Capillary permeability. 3.Protein

More information

Closed-Loop Control of General Anesthesia: My Clinical Experience

Closed-Loop Control of General Anesthesia: My Clinical Experience Closed-Loop Control of General Anesthesia: My Clinical Experience Ngai LIU, M.D. n.liu@hopital-foch.org 33(1)-46-25-27-67 Service d Anesthésie Hôpital Foch Suresnes France JAMA 195, 144 (13) 5 patients,

More information

Childhood Obesity: Anesthetic Implications

Childhood Obesity: Anesthetic Implications Childhood Obesity: Anesthetic Implications The Changing Practice of Anesthesia 2015 UCSF Department of Anesthesia and Perioperative Care Marla Ferschl, MD Associate Professor of Anesthesia University of

More information

Total Intravenous Anesthesia (TIVA) and Target Controlled Infusions (TCI) in Children

Total Intravenous Anesthesia (TIVA) and Target Controlled Infusions (TCI) in Children Curr Anesthesiol Rep (2013) 3:37 41 DOI 10.1007/s40140-012-0005-2 PEDIATRIC ANESTHESIA (J LERMAN, SECTION EDITOR) Total Intravenous Anesthesia (TIVA) and Target Controlled Infusions (TCI) in Children Neil

More information

Are We Safely Dosing Medications in Obese Children? Geisinger Health System Bloomsburg University School of Nurse Anesthesia Kasie Worley, SRNA

Are We Safely Dosing Medications in Obese Children? Geisinger Health System Bloomsburg University School of Nurse Anesthesia Kasie Worley, SRNA Are We Safely Dosing Medications in Obese Children? Geisinger Health System Bloomsburg University School of Nurse Anesthesia Kasie Worley, SRNA Target Objectives Review the basics of pharmacokinetic

More information

OP01 [Mar96] With regards to pethidine s physical properties: A. It has an octanol coefficient of 10 B. It has a pka of 8.4

OP01 [Mar96] With regards to pethidine s physical properties: A. It has an octanol coefficient of 10 B. It has a pka of 8.4 Opioid MCQ OP01 [Mar96] With regards to pethidine s physical properties: A. It has an octanol coefficient of 10 B. It has a pka of 8.4 OP02 [Mar96] Which factor does NOT predispose to bradycardia with

More information

One-Compartment Open Model: Intravenous Bolus Administration:

One-Compartment Open Model: Intravenous Bolus Administration: One-Compartment Open Model: Intravenous Bolus Administration: Introduction The most common and most desirable route of drug administration is orally by mouth using tablets, capsules, or oral solutions.

More information

Implementing receptor theory in PK-PD modeling

Implementing receptor theory in PK-PD modeling Drug in Biophase Drug Receptor Interaction Transduction EFFECT Implementing receptor theory in PK-PD modeling Meindert Danhof & Bart Ploeger PAGE, Marseille, 19 June 2008 Mechanism-based PK-PD modeling

More information

Pharmacology of intravenous anaesthetic drug in hypovolemic shock

Pharmacology of intravenous anaesthetic drug in hypovolemic shock CEEA 2013 Pharmacology of intravenous anaesthetic drug in hypovolemic shock Assoc. Prof. Ioana Grintescu, MD, PhD Assist. Prof. Liliana Mirea, MD, PhD Clinical Emergency Hospital of Bucharest Anaesthesia

More information

Pharmacokinetics. Karim Rafaat

Pharmacokinetics. Karim Rafaat Pharmacokinetics Karim Rafaat Pharmacokinetics The therapeutic effect of a drug is determined by the concentration of drug at the receptor site of action. Even though the concentration of drug that reaches

More information

BASIC PHARMACOKINETICS

BASIC 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 information

Tamer Barakat. Abdul Aziz ALShamali. Abdul Aziz ALShamali

Tamer Barakat. Abdul Aziz ALShamali. Abdul Aziz ALShamali 10 Tamer Barakat Abdul Aziz ALShamali Abdul Aziz ALShamali Dr. Alia Elimination: Refampin is used to treat TB not malaria (Quinacrine is used for malaria) It s the opposite process of absorption. It's

More information

Basic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook with Computer Simulations

Basic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook with Computer Simulations Basic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook with Computer Simulations Rosenbaum, Sara E. ISBN-13: 9780470569061 Table of Contents 1 Introduction to Pharmacokinetics and Pharmacodynamics.

More information

Pharmacokinetics in Drug Development. Edward P. Acosta, PharmD Professor & Director Division of Clinical Pharmacology Director, CCC PK/PD Core

Pharmacokinetics in Drug Development. Edward P. Acosta, PharmD Professor & Director Division of Clinical Pharmacology Director, CCC PK/PD Core Pharmacokinetics in Drug Development Edward P. Acosta, PharmD Professor & Director Division of Clinical Pharmacology Director, CCC PK/PD Core Finding new drugs: A crap shoot Clinical Development Phase

More information

INTRODUCTION TO PHARMACOKINETICS

INTRODUCTION TO PHARMACOKINETICS INTRODUCTION TO PHARMACOKINETICS 1 http://www.biology.iupui.edu/biocourses/biol540/4pipeline2css.html 2 PHARMACOKINETICS 1. ABSORPTION 2. DISTRIBUTION 3. METABOLISM 4. EXCRETION ALL THESE PROCESSES ARE

More information

Hemodynamic Effects of Co-administration of Midazolam during Anesthesia Induction with Propofol and Remifentanil in Hypertensive Patients

Hemodynamic Effects of Co-administration of Midazolam during Anesthesia Induction with Propofol and Remifentanil in Hypertensive Patients https://doi.org/10.7180/kmj.2017.32.1.36 KMJ Original Article Hemodynamic Effects of Co-administration of Midazolam during Anesthesia Induction with Propofol and Remifentanil in Hypertensive Patients Ju

More information

Drug Dosing in Renal Insufficiency. Coralie Therese D. Dimacali, MD College of Medicine University of the Philippines Manila

Drug Dosing in Renal Insufficiency. Coralie Therese D. Dimacali, MD College of Medicine University of the Philippines Manila Drug Dosing in Renal Insufficiency Coralie Therese D. Dimacali, MD College of Medicine University of the Philippines Manila Declaration of Conflict of Interest For today s lecture on Drug Dosing in Renal

More information

AUSTRALIAN PRODUCT INFORMATION REMIFENTANIL APOTEX (REMIFENTANIL HYDROCHLORIDE) POWDER FOR INJECTION

AUSTRALIAN PRODUCT INFORMATION REMIFENTANIL APOTEX (REMIFENTANIL HYDROCHLORIDE) POWDER FOR INJECTION AUSTRALIAN PRODUCT INFORMATION REMIFENTANIL APOTEX (REMIFENTANIL HYDROCHLORIDE) POWDER FOR INJECTION 1 NAME OF THE MEDICINE Remifentanil (as hydrochloride) 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each

More information

Uniformed Services University Nurse Anesthesia Program Anesthesia Pharmacology Note Set

Uniformed Services University Nurse Anesthesia Program Anesthesia Pharmacology Note Set Uniformed Services University Nurse Anesthesia Program Anesthesia Pharmacology Note Set AUGUST, 2004 Fourth Revision i Table of Contents CHAPTER 1: Pharmacokinetic Principles 1 Absorption 2 First Pass

More information

Drug Disposition in Obesity & Protein-Calorie Malnutrition

Drug Disposition in Obesity & Protein-Calorie Malnutrition Drug Disposition in Obesity & Protein-Calorie Malnutrition JBoullata, PharmD, RPh, BCNSP Associate Professor of Pharmacology & Therapeutics -and- Pharmacy Specialist in Nutrition Support University of

More information

Pharmacokinetics of strong opioids. Susan Addie Specialist palliative care pharmacist

Pharmacokinetics of strong opioids. Susan Addie Specialist palliative care pharmacist Pharmacokinetics of strong opioids Susan Addie Specialist palliative care pharmacist What is the difference between pharmacokinetics and pharmacodynamics? Definitions Pharmacokinetics = what the body does

More information

The importance of clearance

The importance of clearance The importance of clearance The calculation of clearance can be especially useful in optimizing dosing of patients The clearance includes both the volume of distribution and the elimination rate The clearance

More information

Paediatric Pharmacology: anaesthetic implications

Paediatric Pharmacology: anaesthetic implications Paediatric Pharmacology: anaesthetic implications Brian Anderson PhD, FANZCA, FCICM Professor Anaesthesiology University of Auckland New Zealand Duccio di Buoninsegna 1308 A Lack of Knowledge of Pharmacology

More information

Pharmacodynamics & Pharmacokinetics 1

Pharmacodynamics & Pharmacokinetics 1 PCTH 325 Pharmacodynamics & Pharmacokinetics 1 Dr. Shabbits jennifer.shabbits@ubc.ca September 9, 2014 Learning objectives 1. Describe the categories of intended drug action 2. Compare and contrast agonists

More information

Comparative study of effective-site target controlled infusion with standard bolus induction of propofol for laryngeal mask airway insertion

Comparative study of effective-site target controlled infusion with standard bolus induction of propofol for laryngeal mask airway insertion Asian Biomedicine Vol. 4 No. 1 February 2010; 177-182 Brief communication (Original) Comparative study of effective-site target controlled infusion with standard bolus induction of propofol for laryngeal

More information

Mark D. Antoszyk, CRNA, BS Director Anesthesia Services Department of Anesthesiology Carolina s Medical Center Northeast Concord, North Carolina

Mark D. Antoszyk, CRNA, BS Director Anesthesia Services Department of Anesthesiology Carolina s Medical Center Northeast Concord, North Carolina Mark D. Antoszyk, CRNA, BS Director Anesthesia Services Department of Anesthesiology Carolina s Medical Center Northeast Concord, North Carolina Mark D. Antoszyk, CRNA, BS, is director of anesthesia services

More information

HST-151 Clinical Pharmacology in the Operating Room

HST-151 Clinical Pharmacology in the Operating Room Harvard-MIT Division of Health Sciences and Technology HST.151: Principles of Pharmocology Instructors: Dr. Carl Rosow, Dr. David Standaert and Prof. Gary Strichartz 1 HST-151 Clinical Pharmacology in

More information

Rational Dose Prediction. Pharmacology. φαρμακον. What does this mean? pharmakon. Medicine Poison Magic Spell

Rational Dose Prediction. Pharmacology. φαρμακον. What does this mean? pharmakon. Medicine Poison Magic Spell 1 Rational Dose Prediction Nick Holford Dept Pharmacology & Clinical Pharmacology University of Auckland, New Zealand 2 Pharmacology Pharmacology is derived from a Greek word (pharmakon). The Greeks used

More information

1. If the MTC is 100 ng/ml and the MEC is 0.12 ng/ml, which of the following dosing regimen(s) are in the therapeutic window?

1. If the MTC is 100 ng/ml and the MEC is 0.12 ng/ml, which of the following dosing regimen(s) are in the therapeutic window? Page 1 PHAR 750: Biopharmaceutics/Pharmacokinetics October 23, 2009 - Form 1 Name: Total 100 points Please choose the BEST answer of those provided. For numerical answers, choose none of the above if your

More information

Name: UFID: PHA Exam 2. Spring 2013

Name: UFID: PHA Exam 2. Spring 2013 PHA 5128 Exam 2 Spring 2013 1 Carbamazepine (5 points) 2 Theophylline (10 points) 3 Gentamicin (10 points) 4 Drug-drug interaction (5 points) 5 Lidocaine (5 points) 6 Cyclosporine (5 points) 7 Phenobarbital

More information

Basic Concepts of TDM

Basic Concepts of TDM TDM Lecture 1 5 th stage What is TDM? Basic Concepts of TDM Therapeutic drug monitoring (TDM) is a branch of clinical pharmacology that specializes in the measurement of medication concentrations in blood.

More information

PHA 5128 Final Exam Spring 2004 Version A. On my honor, I have neither given nor received unauthorized aid in doing this assignment.

PHA 5128 Final Exam Spring 2004 Version A. On my honor, I have neither given nor received unauthorized aid in doing this assignment. PHA 5128 Final Exam Spring 2004 Version A On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name There are 18 questions. Total /120 pts Final 2004 1 1. T.P., a 66-year-old,

More information

General Principles of Pharmacology and Toxicology

General Principles of Pharmacology and Toxicology General Principles of Pharmacology and Toxicology Parisa Gazerani, Pharm D, PhD Assistant Professor Center for Sensory-Motor Interaction (SMI) Department of Health Science and Technology Aalborg University

More information

Basic Concepts in Pharmacokinetics. Leon Aarons Manchester Pharmacy School University of Manchester

Basic Concepts in Pharmacokinetics. Leon Aarons Manchester Pharmacy School University of Manchester Basic Concepts in Pharmacokinetics Leon Aarons Manchester Pharmacy School University of Manchester Objectives 1. Define pharmacokinetics 2. Describe absorption 3. Describe distribution 4. Describe elimination

More information

8/26/14. Disclosures. Objectives. None

8/26/14. Disclosures. Objectives. None Disclosures None Objectives Understand Importance of Pediatric Obesity Impact on Physiology Preoperative Assessment Intra-operative Management PACU & the obese pediatric Patient 1 Gender specific charts

More information

PHA Final Exam Fall 2001

PHA Final Exam Fall 2001 PHA 5127 Final Exam Fall 2001 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Question/Points 1. /12 pts 2. /8 pts 3. /12 pts 4. /20 pts 5. /27 pts 6. /15

More information

Introduction to Pharmacokinetics (PK) Anson K. Abraham, Ph.D. Associate Principal Scientist, PPDM- QP2 Merck & Co. Inc., West Point, PA 5- June- 2017

Introduction to Pharmacokinetics (PK) Anson K. Abraham, Ph.D. Associate Principal Scientist, PPDM- QP2 Merck & Co. Inc., West Point, PA 5- June- 2017 Introduction to Pharmacokinetics (PK) Anson K. Abraham, Ph.D. Associate Principal Scientist, PPDM- QP2 Merck & Co. Inc., West Point, PA 5- June- 2017 1 Outline Definition & Relevance of Pharmacokinetics

More information

PHA Final Exam Fall 2006

PHA Final Exam Fall 2006 PHA 5127 Final Exam Fall 2006 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Please transfer the answers onto the bubble sheet. The question number refers

More information

Pharmacokinetics PCTH 325. Dr. Shabbits September 12, C t = C 0 e -kt. Learning Objectives

Pharmacokinetics PCTH 325. Dr. Shabbits September 12, C t = C 0 e -kt. Learning Objectives PCTH 325 Pharmacokinetics Dr. Shabbits jennifer.shabbits@ubc.ca September 12, 2013 Learning Objectives 1. Interpret Concentration vs graphs and use them to calculate half life and predict drug concentration

More information

Introduction to. Pharmacokinetics. University of Hawai i Hilo Pre-Nursing Program NURS 203 General Pharmacology Danita Narciso Pharm D

Introduction 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 information

Pharmacokinetics of propofol when given by intravenous

Pharmacokinetics of propofol when given by intravenous Br. J. clin. Pharmac. (199), 3, 144-148 Pharmacokinetics of propofol when given by intravenous infusion DENIS J. MORGAN', GWEN A. CAMPBELL2,* & DAVID P. CRANKSHAW2 'Victorian College of Pharmacy, 381 Royal

More information

Effect-site concentration of remifentanil for laryngeal mask airway insertion during target-controlled infusion of propofol

Effect-site concentration of remifentanil for laryngeal mask airway insertion during target-controlled infusion of propofol doi:10.1111/j.1365-2044.2008.05707.x Effect-site concentration of remifentanil for laryngeal mask airway insertion during target-controlled infusion of propofol M. K. Kim, 1 J. W. Lee, 2 D. J. Jang, 3

More information

Synergism between rocuronium and cisatracurium: comparison of the Minto and Greco interaction models

Synergism between rocuronium and cisatracurium: comparison of the Minto and Greco interaction models KJA Korean Journal of Anesthesiology Clinical Research Article pissn 25-6419 eissn 25-7563 Synergism between rocuronium and cisatracurium: comparison of the Minto and Greco interaction models Soeun Jeon

More information

Drug dosing in Extremes of Weight

Drug dosing in Extremes of Weight Drug dosing in Extremes of Weight The Plump & Heavy versus The Skinny & Light Maria Minerva P. Calimag, MD, MSc, PhD, DPBA, FPSECP PROFESSOR Departments of Pharmacology, Anesthesiology and Clinical Epidemiology

More information

Renal Function. 1. Glomerular filtration 2. Active tubular secretion 3. Passive tubular reabsorption 4. Excretion

Renal Function. 1. Glomerular filtration 2. Active tubular secretion 3. Passive tubular reabsorption 4. Excretion 59-291 Section 1, Lecture 5 Drug Excretion -most drugs are excreted in urine either as unchanged or drug metabolites Renal Function 1. Glomerular filtration 2. Active tubular secretion 3. Passive tubular

More information

PHA Final Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

PHA Final Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment. PHA 5127 Final Exam Fall 2010 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Please transfer the answers onto the bubble sheet. The question number refers

More information

Sedation For Cardiac Procedures A Review of

Sedation For Cardiac Procedures A Review of Sedation For Cardiac Procedures A Review of Sedative Agents Dr Simon Chan Consultant Anaesthesiologist Department of Anaesthesia and Intensive Care Prince of Wales Hospital Hong Kong 21 February 2009 Aims

More information

Adult Care Plan Allergies: Date / / OR. Anesthesia Technique. Airway Mal / SMS FB / TMJ / CS / Teeth. Induction Agents

Adult Care Plan Allergies: Date / / OR. Anesthesia Technique. Airway Mal / SMS FB / TMJ / CS / Teeth. Induction Agents Adult Care Plan Allergies: Date / / OR Name Age Ht Wt BSA ASAClass Procedure Time Position CRNA Anesthesiologist Surgeon Medical / Surgical History Current Medications Preoperative Labs EKG CXR Preoperative

More information

INTRODUCTION. Although propofol is an intravenous anesthe tic commonly used for anesthesia in morbidly obese. (Acta Anaesth. Belg.

INTRODUCTION. Although propofol is an intravenous anesthe tic commonly used for anesthesia in morbidly obese. (Acta Anaesth. Belg. (Acta Anaesth. Belg., 211, 62, 73-82) Maintenance of anesthesia in morbidly obese patients using propofol with continuous BIS-monitoring : a comparison of propofol-remifentanil and propofol-epidural anesthesia

More information

Total Intravenous Anaesthesia

Total Intravenous Anaesthesia Total Intravenous Anaesthesia Balasubramanian Thiagarajan Stanley Medical College Abstract: Total intravenous anaesthesia (TIVA) is a technique of anaesthesia which involves use of intravenous drugs to

More information

Biomath M263 Clinical Pharmacology

Biomath M263 Clinical Pharmacology Training Program in Translational Science Biomath M263 Clinical Pharmacology Spring 2013 www.ctsi.ucla.edu/education/training/webcasts Wednesdays 3 PM room 17-187 CHS 4/3/2013 Pharmacokinetics and Pharmacodynamics

More information

TDM. Measurement techniques used to determine cyclosporine level include:

TDM. Measurement techniques used to determine cyclosporine level include: TDM Lecture 15: Cyclosporine. Cyclosporine is a cyclic polypeptide medication with immunosuppressant effect. It has the ability to block the production of interleukin-2 and other cytokines by T-lymphocytes.

More information

Pharmacology of intravenous induction agents

Pharmacology of intravenous induction agents Pharmacology of intravenous induction agents Ákos Csomós MD, PhD Professor, Head of Department Medical Centre, Hungarian Defence Force, Budapest What do we have in the market? Thiopental Metohexital Etomidate

More information

British Journal of Anaesthesia 100 (1): (2008) doi: /bja/aem279 Advance Access publication November 23, 2007 Remifentanil target-controll

British Journal of Anaesthesia 100 (1): (2008) doi: /bja/aem279 Advance Access publication November 23, 2007 Remifentanil target-controll British Journal of Anaesthesia 100 (1): 125 30 (2008) doi:10.1093/bja/aem279 Advance Access publication November 23, 2007 Remifentanil target-controlled infusion vs propofol targetcontrolled infusion for

More information

Delayed Drug Effects. Distribution to Effect Site. Physiological Intermediate

Delayed Drug Effects. Distribution to Effect Site. Physiological Intermediate 1 Pharmacodynamics Delayed Drug Effects In reality all drug effects are delayed in relation to plasma drug concentrations. Some drug actions e.g. anti-thrombin III binding and inhibition of Factor Xa by

More information

Pharmacokinetics Overview

Pharmacokinetics Overview Pharmacokinetics Overview Disclaimer: This handout and the associated lectures are intended as a very superficial overview of pharmacokinetics. Summary of Important Terms and Concepts - Absorption, peak

More information

BIS Monitoring. ASSESSMENT OF DEPTH OF ANAESTHESIA. Why measure depth of anaesthesia? or how to avoid. awareness in one easy lesson

BIS Monitoring.   ASSESSMENT OF DEPTH OF ANAESTHESIA. Why measure depth of anaesthesia? or how to avoid. awareness in one easy lesson BIS Monitoring or how to avoid www.eurosiva.org awareness in one easy lesson ASSESSMENT MONITORING ANAESTHETIC DEPTH OF DEPTH OF ANAESTHESIA Why measure depth of anaesthesia? How do the various EEG monitors

More information

Total Intravenous Anesthesia

Total Intravenous Anesthesia Total Intravenous Anesthesia A RATIONAL APPROACH TO ANESTHETIC MANAGEMENT Michael Rieker, DNP, CRNA, FAAN Director, Nurse Anesthesia Program Wake Forest School of Medicine Objectives Review drugs and methods

More information

Pharmacokinetic Modeling & Simulation in Discovery and non-clinical Development

Pharmacokinetic 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 information

PHA Spring First Exam. 8 Aminoglycosides (5 points)

PHA Spring First Exam. 8 Aminoglycosides (5 points) PHA 5128 Spring 2012 First Exam 1 Aminoglycosides (5 points) 2 Aminoglycosides (10 points) 3 Basic Principles (5 points) 4 Basic Principles (5 points) 5 Bioavailability (5 points) 6 Vancomycin (5 points)

More information

Section 5.2: Pharmacokinetic properties

Section 5.2: Pharmacokinetic properties Section 5.2: Pharmacokinetic properties SmPC training presentation Note: for full information refer to the European Commission s Guideline on summary of product characteristics (SmPC) SmPC Advisory Group

More information

CHAPTER 11. General and Local Anesthetics. Anesthetics. Anesthesia. Eliza Rivera-Mitu, RN, MSN NDEG 26 A

CHAPTER 11. General and Local Anesthetics. Anesthetics. Anesthesia. Eliza Rivera-Mitu, RN, MSN NDEG 26 A CHAPTER 11 General and Local Anesthetics Eliza Rivera-Mitu, RN, MSN NDEG 26 A Anesthetics Agents that depress the central nervous system (CNS) Depression of consciousness Loss of responsiveness to sensory

More information

PHA Second Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

PHA Second Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment. PHA 5127 Second Exam Fall 2012 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Put all answers on the bubble sheet TOTAL /150 pts 1 Question Set I (True or

More information

Usefulness of Intravenous Anesthesia Using a Targetcontrolled Infusion System with Local Anesthesia in Submuscular Breast Augmentation Surgery

Usefulness of Intravenous Anesthesia Using a Targetcontrolled Infusion System with Local Anesthesia in Submuscular Breast Augmentation Surgery Usefulness of Intravenous Anesthesia Using a Targetcontrolled Infusion System with Local Anesthesia in Submuscular Breast Augmentation Surgery Original Article Kyu-Jin Chung 1, Kyu-Ho Cha 2, Jun-Ho Lee

More information

Analgesic-Sedatives Drug Dose Onset

Analgesic-Sedatives Drug Dose Onset Table 4. Commonly used medications in procedural sedation and analgesia Analgesic-Sedatives Fentanyl Morphine IV: 1-2 mcg/kg Titrate 1 mcg/kg q3-5 minutes prn IN: 2 mcg/kg Nebulized: 3 mcg/kg IV: 0.05-0.15

More information

ADME Review. Dr. Joe Ritter Associate Professor of Pharmacology

ADME Review. Dr. Joe Ritter Associate Professor of Pharmacology ADME Review Dr. Joe Ritter Associate Professor of Pharmacology 828-1022 jkritter@vcu.edu What percent of a weak base (pka = 7.5) and weak acid (pka = 3.5) will be respectively ionized in urine of ph 5.5?

More information

PHARMACOKINETICS OF MIDAZOLAM IN TOTAL I.V. ANAESTHESIA

PHARMACOKINETICS OF MIDAZOLAM IN TOTAL I.V. ANAESTHESIA Br. J. Anaesth. (1987), 59, 548-556 PHARMACOKINETICS OF MIDAZOLAM IN TOTAL I.V. ANAESTHESIA P. PERSSON, A. NILSSON, P. HARTVIG AND A. TAMSEN Total i.v. anaesthesia, defined as anaesthesia provided solely

More information

PHA Second Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

PHA Second Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment. PHA 5127 Second Exam Fall 2011 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Put all answers on the bubble sheet TOTAL /200 pts 1 Question Set I (True or

More information

Monitoring cortical electrical activity in anesthesia for obese patient

Monitoring cortical electrical activity in anesthesia for obese patient Monitoring cortical electrical activity in anesthesia for obese patient Gabriel M. Gurman, M.D. Division of Anesthesiology Soroka Medical Center and Faculty of Health Sciences, Ben Gurion University Beer

More information

TRANSPARENCY COMMITTEE OPINION. 21 January 2009

TRANSPARENCY COMMITTEE OPINION. 21 January 2009 The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION 21 January 2009 BRIDION 100 mg/ml, solution for injection Box containing 10 x 2 ml bottles, CIP: 573 553-9 Box containing

More information

PHA Second Exam Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

PHA Second Exam Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment. PHA 5127 Second Exam Fall 2013 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Question/Points Set I 20 pts Set II 20 pts Set III 20 pts Set IV 20 pts Set

More information