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The following courses are offered by the PKDM Unit:


Within the 5-year M.Sc(Pharm) programme:

Within the 3-year B.Sc(Pharm) (Prescriptionist) programme:

 

 

Courses within the MSc(Pharm) programme (Apotekarprogrammet)

Pharmacokinetics and drug metabolism

Code: PKM630

Level: Advanced Level 1

Duration: 8 full-time weeks (12 ECTS)

Normal calendar time: April - June

Grades: Fail, Pass, Pass with distinction (3 tiers)

Description: An in-depth course covering preclinical and clinical pharmacokinetics (PK), drug metabolism (DM) and pharmacodynamics (PD). In contrast to course KFK010, this slightly more demanding course also covers preclinical aspects, and places more emphasis on drug metabolism and data analysis.

Objectives: The student shall reach a clear understanding of the processes governing the rate and degree of absorption, distribution and elimination of drugs and other xenobiotics in the body (pharmacokinetics), and how these processes affect the intensity and duration of drug response (pharmacodynamics). The student shall be able to apply such knowledge to analyse and interpret preclinical and clinical data. The student shall be confident with both non-compartmental as well as compartmental analysis. The general principles of drug metabolism shall be understood. The student shall understand reasons for choosing dosing strategies for optimizing drug therapy. Emphasis is placed on the causes and expression of individual variability in drug absorption and disposition. The student shall be able to understand and interpret qualified pharmacokinetic information and after critical review be able to provide such information to others.

Contents:

Theory:

• Estimation of PK parameters after intravenous bolus dose (compartment models)
• Drug absorption and bioavailability
• In vitro and in vivo methods to study drug absorption
• Biopharmaceutics
• Absorption kinetics
• Drug transport and distribution in the body
• Plasma protein binding
• Elimination
• Clearance and extraction models
• Hepatic drug elimination
• Renal drug elimination
• Repeated drug administration, dosage strategies
• Drug metabolism
• Enzyme localization, taxonomy and reactions
• Regulation of DM enzymes
• In vitro methods
• Metabolite kinetics
• In vivo methods to study drug metabolism
• Non-linear kinetics
• Pharmacodynamics
• Integration of pharmacokinetic concepts with physiology
• PK data analysis: introduction to modeling by non-linear regression
• Variability in PKPD
• Mechanisms for drug-drug interactions
• PKPD aspects in preclinical drug development
• PKPD aspects in clinical drug development


Practical work:

1. Comparison of the estimation of Michaelis-Menten parameters from in vitro drug metabolism data using linear transforms (Lineweaver-Burke, Eadie-Hofstee, Hanes-Wolff using Excel®) and by non-linear regression output for depletion and formation rate data. Model discrimination between single and multiple metabolic pathways.

2. Hands-on application of non-linear regression software WinNonlin® on PK compartment modeling. Model discrimination and simulation from single to repeated dose.

3. Analysis and interpretation of PKPD data from a series of studies included in a hypothetical New Drug Application ("Zamavica").

Workshops:

A series of 8 - 10 tutorial 3-hr workshops in which the students solve problems by discussion and/or calculation are an important part of the course. These supervised workshops facilitate the understanding of the course contents taught and how it may be applied.

Examples of literature:

Rowland M & Tozer TN: Clinical pharmacokinetics – concepts and applications, Lippincott, Williams & Wilkins

Alternative recommended literature:
Kwon Y: Handbook of Essential Pharmacokinetics, Pharmacodynamics, and Drug Metabolism for Industrial Scientists, Kluwer Academic, Plenum publishers

Ashton M: Problemsamling i farmakokinetik.

NB. The above description is an extension of the formal, briefer Course Plan approved by the Sahlgrenska Academy.

Drug Toxicology and Toxicokinetics

Code: TOX640

Level: Advanced Level 1

Duration: 2 full-time weeks (3 ECTS)

Normal calendar time: May

Grades: Fail, Pass (2 tiers)

Description: The course is required in the M.Sc.(Pharm) programme. The course is normally held in Swedish but could be provided in the English language.

Objectives: The student shall upon completion of the course have obtained a good understanding of the toxicological studies performed in support of a marketing approval application of a new chemical entity.

Contents:

Theory:

Drug Toxicology

Toxicology in the drug development process, carcinogenicity, genotoxicity, embryotoxicology, teratogenicity, reproduction toxicology, immunotoxicology, imaging techniques (autoradiography), safety pharmacology.

Toxicokinetics

Cross-species comparison of exposure, Dawson's formula, species differences in drug absorption, distribution and drug metabolism, allometric scaling.


Literature:

Mulder & Dencker, Pharmaceutical Toxicology, Pharmaceutical Press,

Lu F, Kacew S : Lu's Basic Toxicology: Fundamentals. Target Organs and Risk Assessment, Taylor & Francis

ICH safety guidelines: S1-S8 and M3

Ejlertsson G: Statistik för hälsovetenskaperna, Studentlitteratur, Lund

Läkemedelsboken, chapters: läkemedelsbiverkningar, porfyri och läkemedel, läkemedel i miljön, förgiftningar, Apoteket AB

Alternative recommended literature:

Klaassen C, Watkins J: Essentials of Toxicology, The McGraw-Hill Companies

Altman DG: Practical Statistics for Medical Research, Chapman & Hall


NB. The above description is an extension of the formal, briefer Course Plan approved by the Sahlgrenska Academy.

Pharmacotherapeutics/Farmakoterapi

Code: FAT730

Level: Advanced level 1

Duration: 5 full-time weeks (7.5 ECTS)

Normal calendar time: December – January

Grades: Fail, Pass, Pass with distinction (3 tiers)

Description: This course is required in the MSc(Pharm) Programme. The course is normally held in Swedish but could be provided in English.

Objectives: The course focuses primarily on the pharmacological treatment of diseases. The most common illnesses in outpatient and inpatient care will be discussed with a focus on the following areas: cardiovascular, depression, anxiety and sleep, pain, infection, gastro-intestinal, asthma, COPD, allergy.

The student should upon completion of the course have obtained a good understanding of therapy and treatment recommendations for the different disease areas. The student should have gained knowledge about the most common drug groups and drug names within a treatment area. The students will obtain knowledge and understanding of the most common side effects, pharmacokinetics and interactions of the medicines that are discussed during the course.

Contents

Theory:
• symptoms of the diseases
• identification of the disease based on laboratory values
• treatment areas for the different drug groups
• pharmacokinetics of the drug groups
• mechanisms of action
• interactions and side effects of the drug groups
• treatment strategies and therapeutic recommendations
• interpretation of laboratory tests to evaluate and adapt a current drug therapy
• comparison of different treatments for a disease
• individualised dosage regimens in special populations such as children, the elderly and patients suffering from renal, cardiovascular, hepatic and other disease

Project work including oral presentation:
One week is entirely devoted to problem-based learning. The students work independently and discuss real-world patient cases in the form of summary descriptions with history, symptoms, laboratory values and drug treatment given. Based on these data, side effects and interactions are evaluated, and the students justify whether any changes in drug therapy is necessary.
The evaluated patient cases are then reported orally at a seminar.

Workshops: 2 tutorial 3-hr workshops in which the students solve problems by discussion and/or calculation. These supervised workshops facilitate the understanding of the course contents taught on dosing and asthma / COPD.

Literature, examples:

Blom A, Carlsson J, Söderlund BM, Laurells klinisk kemi i praktisk medicin
Rowland M and Tozer TN, Clinical Pharmacokinetics – concepts and applications
Läkemedelsboken 2009-2010, Apoteket AB
FASS 2009, LIF
Lindskog B, Medicinsk miniordbok
Therapy recommendations, most of which are web-based, for example therapy recommendations Halland County Council, COR list Västra Götaland Region, Skåne County list, Wise List Stockhol County Council
Web-based materials including the MPA and SBU
Koda-Kimble MA, Applied Therapeutics

 

Preclinical Drug Development

Code: FAB810

Level: Advanced level 2

Duration: 5 full-time weeks (7.5 ECTS)

Normal calendar time: February

Grades: Fail, Pass (2 tiers)

Description: This advanced level, elective course is offered within the MSc(Pharm) programme. It can be offered in either the Swedish or English language. The course builds upon PKM630.

Objectives: To give the student in-depth knowledge of preclinical drug development, with focus on xenobiotic metabolism and pharmacokinetics. It aims to provide knowledge and skills needed for future work within drug development and research. A main objective of the course is to provide knowledge of how assessment of absorption, distribution, metabolism and elimination contribute to rational drug development. There are two themes throughout the course: bioanalytical chemistry and drug metabolism/pharmacokinetics/ - and pharmacokinetic/-dynamics. Data analysis is also a strong component.

Contents

Theory:

Bioanalytical chemistry:

Calibration, chromatographic theory, liquid/gas/capillary electroforesis chromatography, preparation and clean-up of biological samples.

Drug metabolism/pharmacokinetics/-dynamics:
Experimental systems (sub-/cellular systems, organ preparations, in vivo) for preclinical characterization of xenobiotic biotransformation, including methods for identification of metabolite structure, metabolizing enzymes and potential for drug-drug interactions. Reactive metabolites. In silico modeling of drug metabolism (QSAR etc). Physiologically based pharmacokinetic models. Pharmacokinetic/-dynamic modeling.

Practical work:

Experimental:

One week is entirely devoted to practical work, in which the following experiments are performed:

1. In vitro metabolism of chloramphenicol in rat liver microsomal incubations at varying initial substrate concentrations. Quantitation of chloramphenicol and its major metabolite by reversed phase ion-pair high performance liquid chromatography. Estimation of Michaelis-Menten parameters by modeling obtained depletion (and metabolite formation) concentration-time data (WinNonlin®). Discrimination of competing kinetic models.

2. Determination of salicylic acid protein binding to serum albumin by ultrafiltration under varying concentrations of ligand, protein and free fatty acids. Quantitation of drug concentrations by high performance liquid chromatography. Estimation of Scatchard model parameters by modeling total vs unbound salicylate concentrations (WinNonlin®). Discrimination of competing binding models.

3. Simulation of blood and tissue concentration-time profiles with a physiologically based pharmacokinetic (PBPK) model in which different conditions are tested. The model is built and run in ACSLXtreme®.

Data analysis:

1. Experimental chromatographic data are processed in CSW and results explored and modeled in Excel® and/or WinNonlin®. Each student is required to write a 20-page report summarizing the experimental work as main part of the examination.

2. A major excercise throughout the course involves the selection of one out of three drug candidate compounds based on their preclinical characteristics. The data available is a condensation of physicochemical, permeability, drug metabolic and animal in vivo PKPD properties.

Workshops:

Chromatography and bioanalysis; hands-on pharmacokinetic-pharmacodynamic modelling (WinNonlin®).

Literature:
Atkinson AJ Jr , Abernethy DR, Daniels CE, Dedrick R, Sanford P. Markey SP, Principles of Clinical Pharmacology, Academic Press; 2 edition.
Renman L: Instrumentella Separationsmetoder: Kromatografi och Kapillärelektrofores

Alternative recommended literature:
Schoenwald R D: Pharmacokinetics in Drug Discovery and Development, CRC Press
Kwon Y: Handbook of Essential Pharmacokinetics, Pharmacodynamics, and Drug Metabolism for Industrial Scientists, Kluwer Academic/Plenum Publishers
Smith D A, van de Waterbeemd H, Walker DK: Pharmacokinetics and Metabolism in Drug Design, Wiley-VCH
NB. The above description is an extension of the formal, briefer Course Plan approved by the Sahlgrenska Academy.

Clinical Pharmacokinetics and Pharmacodynamics

Code: FAB820

Level: Advanced Level 2

Duration: 5 full-time weeks (7.5 ECTS)

Normal calendar time: May - June 7

Grades: Fail, Approved (2 tiers)

Description: An elective course within the MSc(Pharm) programme, being an ultimate theoretical course in that programme. It can be offered in either the Swedish or English language. The course builds upon PKM630.

Objectives: After completion of the course the student shall have in-depth knowledge of drug absorption, distribution, metabolism and elimination in humans as well as how these processes impact on the intensity and duration of drug response. The student shall be confident with data analysis of experimental results. Further, the student shall have an understanding of the clinical drug development process including issues relating to the design, planning and conduct of explanatory and confirmative clinical studies. The student shall acquire specialised knowledge on the optimal use of specific drugs. The course aims to provide the student knowledge and skills of importance for future work within clinical drug development and/or clinically oriented pharmacy.

Contents

Within clinical drug development the course covers:

Clinical trial methodology

The clinical development plan and the design of 'First-time-in-man' studies, ADME, DD interaction studies, dose-finding studies.

International guidelines with general impact on the clinical drug development process

Theory of and hands-on experience (WinNonlin® software) with pharmacokinetic-pharmacodynamic modelling, including introduction to population (non-linear mixed effects) analysis.

Within clinical drug use (pharmacotherapy) the course covers:

Causes of inter- and intra-individual pharmacokinetic/pharmacodynamic variability and optimisation of drug treatment with respect to such variability.

Individualised dosage regimens in special populations such as children, the elderly and patients suffering from renal, cardiovascular, hepatic and other disease.

Practical coursework

1. Comparison of non-compartmental and compartmental analysis using WinNonlin® with authentic data from a Phase I study on furosemide kinetics and dynamics after intravenous and oral single-doses in a food-drug interaction cross-over study. The preparation of a study report in the English language is an integral part of examination.

2. Pharmacokinetic-pharmacodynamic modelling using the WinNonlin® library.

3. Drafting a clinical development plan for a candidate drug (group exercise).

4. Design of Phase I, II and III studies based on results obtained by trial simulation in RIDO® software (group excercise).

5. Problem-solving workshops with calculation of individualised dosage regimens for selected drugs and clinical situations.

6. How to read a clinical study report (scientific article).

7. Determination of caffeine population pharmacokinetics after dietary intake, based on sparse saliva sampling, quantitation by HPLC and data analysis in Nonmem®.

8. Research for and delivery of oral presentation on the pharmacokinetics/-dynamics and the particular pharmacotherapeutic problems associated with one of a number of selected therapies (group work). The presentation is part of the examination process.

Course Literature

Atkinson AJ Jr, Abernethy DR, Daniels CE, Dedrick R, Sanford P. Markey SP, Principles of Clinical Pharmacology, Academic Press; 2 edition.

ICH Guidelines, Efficacy Topics

In addition, scientific articles and reference literature.

Alternative literature:

Schoenwald R, Pharmacokinetics in Drug Discovery and Development (CRC Press 2002).

Bauer LA, Applied Clinical Pharmacokinetics, McGraw-Hill 2001

Gabrielsson J and Weiner D, Pharmacokinetic and Pharmacodynamic Data Analysis, Apotekarsocietetens förlag, Stockholm (ISBN: 9186274929)

Winter ME, Basic Clinical Pharmacokinetics, Lippincott Williams & Wilkins 2004


NB: The above description is an extension of the formal, briefer Course Plan approved by the Sahlgrenska Academy.

Degree research project

Code: xxxxx

Level: Advanced level 2

Duration: 20 full-time weeks (30 ECTS)

Normal calendar time: September – mid-January

Grades: Fail, Approved (2 tiers)

Description:

Link: /xxx/

 

Courses within the BSc(Pharm) programme (Receptarieprogrammet)

 

Clinical Pharmacokinetics/Klinisk farmakokinetik

Code: KFK200

Level: Basic level

Duration: 7 full-time weeks (10.5 ECTS)

Normal calendar time: mid-September – mid-November

Grades: Fail, Approved, With Distinction (3 tiers)

Description: A introductory course in pharmacokinetics with clinical orientation within the Prescriptionist (BSc(Pharm)) programme in its 3rd year. This course is held in the Swedish language only.

Course description (Swedish):
Förkunskapskrav
Till behörighet till kursen fordras att receptarieprogrammets första xx hp omfattande Introduktionskurs, 7.5 hp, Farmaceutisk kemi, 22.5 hp, Cellbiologi, 15 hp, Integrativ biomedicin I, II, III, IV om sammanlagt 45 hp, Läkemedels ursprung, struktur och toxikologi, 15 hp, Galenisk farmaci 7.5 hp, Samhällsfarmaci, 7.5 hp, Författningar, 4.5 hp, eller motsvarande är genomgångna.
4. Innehåll
Deskriptiv farmakokinetik med fokus på enklare modeller för läkemedels absorptionskinetik och disposition. Definition av centrala begrepp såsom fördelningsvolym, clearance, biotillgänglighet samt hur dessa kan beräknas.
Hur läkemedel upptas efter extravaskulär, ffa oral, administrering; mekanismer för absorption och vilka faktorer inverkar på såväl absorptionens grad som hastighet (läkemedlets fysikalisk-kemiska egenskaper i samspel med mag-tarmkanalens fysiologi, transittider, inverkan av födoämnen, beredningsform, dos, transportprotein och metabolism).

Processer med vilka läkemedel och andra kroppsfrämmande ämnen elimineras hos människa (metabolism, renal och biliär utsöndring) samt hur dessa experimentellt kan kvantifieras och karakteriseras. Hur de viktigaste läkemedelsmetaboliserande enzymen omvandlar xenobiotika samt hur kapaciteten hos dessa enzym styrs av genetiska faktorer och regleras av miljöfaktorer. Basal behandling av metaboliters dispositionskinetik.
Matematiska modeller för läkemedels fördelning samt elimination i organ och andra vävnader. Hur läkemedels bindning till plasmaprotein påverkar farmakokinetik och tolkningen av experimentella (kliniska) resultat samt beskrivning av experimentella metoder för bestämning av plasmaproteinbindning.

Samband mellan läkemedelsexposition och effektens intensitet och kinetik där sådan är att förvänta samt anledningar till varför uppenbara samband ibland saknas. Basala modeller inkl. sigmoid Emax-modell samt definition av terapeutiskt koncentrationsintervall.
Beräkning av doser och doseringsintervall för enskilda läkemedel efter olika administreringssätt på basis av kunskap om substansens farmakokinetik och farmakodynamik.
Orsaker till farmakokinetisk och farmakodynamisk variabilitet i en (patient-) population och hur dessa kommer till uttryck beroende på ålder, kön, läkemedelsinteraktioner, sjukdom samt genetiskt arv. Speciellt behandlas dosering till barn samt äldre, inhiberingsinteraktioner samt dosering vid nedsatt njurfunktion. Konceptet individualiserad läkemedelsbehandling samt översiktligt om terapeutisk läkemedelskontroll.
Speciella aspekter vad avser behandling med läkemedel med problematisk eller komplex farmakokinetik, ex.vis dos- eller tidsberoende kinetik, aktiva metaboliter, kiralitet.
Undervisningen sker i form av föreläsningar och gruppdiskussioner. En fördjupningsuppgift ingår som obligatoriskt moment. Datorövningar och laborationer kan förekomma men är ej obligatoriska.

5. Mål
Efter avslutat kurs skall studenten
- kunna redovisa god kunskap om de processer som styr hastigheten och graden för läkemedels - och andra kroppsfrämmande ämnens - upptag, fördelning och elimination i kroppen (farmakokinetik) samt hur dessa påverkar effektens intensitet och tidsförlopp (farmakodynamik)
- kunna beräkna primära och sekundära farmakokinetiska parametrar utifrån koncentration- och utsöndringsdata och och tolka innebörden av beräknade värden
- ha basala kunskaper om beredningsformens betydelse för absorptionens grad och kinetik (biofarmaci)
- utifrån ett läkemedels exposition-responssamband kunna förutsäga effektens intensitet, duration samt terapeutiskt index
- förstå olika grunder för val av doseringsstrategier i syfte att optimera läkemedelsbehandling.
- kunna prediktera och värdera risker för läkemedelsinteraktioner på farmakokinetisk/metabol nivå.
- kunna utläsa och tolka farmakokinetisk information ur tabeller, grafer och fackmässig text och efter kritisk granskning kunna förmedla sådan information till andra.

6. Kurslitteratur
Se separat litteraturlista.

7. Former för bedömning
Examination sker genom skriftlig tentamen omfattande 10.5 hp. För att erhålla betyg över hel kurs skall studenten nöjaktigt ha redovisat erhållen fördjupningsuppgift.

För studerande som ej blivit godkänd vid ordinarie prov erbjuds ytterligare fyra provtillfällen. Student äger rätt till byte av examinator efter attha underkänts två gånger på samma examination, om det är praktiskt möjligt. En sådan begäran ställs till institutionen och skall vara skriftlig.

8. Betyg
Betygsskalan omfattar betygsgraderna Underkänd (U), Godkänd (G) och Väl godkänd (VG).

Om ECTS-betyg önskas skall detta skriftligen anmälas till kursansvarig senast en vecka efter kursstart.

9. Kursvärdering
Under pågående kurs hålls kursråd och efter avslutat kurs genomförs en skriftlig kursutvärdering. Sammanställningar av dessa förmedlas till programråd 3 vid Sahlgrenska akademin och receptariekansliet. Sammanställningarna utgör underlag vid planering av påföljande kurstillfälle.

10. Övrigt
Kursen ersätter kurs KFK010 och kurserna kan inte tillgodoräknas samtidigt i en examen.

Litteraturlista KFKxxx, Klinisk farmakokinetik, 10,5 hp.

Tozer T.N. & Rowland M, Introduction to pharmacokinetics and pharmacodynamics – the quantitative basis of drug therapy

Kurskompendier och annat utdelat material.

Alternativ litteratur
Birkett, D.J. Pharmacokinetics made easy

Rowland M & Tozer T.N. Clinical pharmacokinetics – concepts and applications


Degree research project

Code: xxxxx

Level: Advanced level 1?

Duration: 10 full-time weeks (15 ECTS) or 20 full-time weeks (30 ECTS)

Normal calendar time: mid-January – March, or April – June

Grades: Fail, Approved, With Distinction (3 tiers) /since 2009?/

Description:

Link: /xxx/

 

Contact Information

Michael Ashton

Box 431 , 405 30 Göteborg

Visiting Address:
Medicinaregatan 13A

Phone:
+46 (0)31 786 34 12

Fax:
+46 (0)31 786 32 84

Page Manager: Webbredaktör|Last update: 12/14/2016
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