Pharmaceutical Medicine - uitgebreide samenvatting
0 purchase
Course
Pharmaceutical Medicine (E03N9A)
Institution
Katholieke Universiteit Leuven (KU Leuven)
Uitgebreide samenvatting van het vak Pharmaceutical Medicine gegeven in 1ste master Biomedische Wetenschappen. In combinatie met de beknopte samenvatting behaalde ik een 15/20 in eerste zit. Combinatie van slides, notities, figuren/tekeningen zoals gezien in de les.
1. CLINICAL PHARMACOLOGY AND PHARMACOKINETICS .....................................................................................................3
1.1. Basic concepts (Les 1) ..................................................................................................................................................3
1.2. Clinical pharmacology in special populations (Les 12) ................................................................................................5
1.2.2. Neonates, children ...............................................................................................................................................5
1.2.3. Pregnancy and lactation, geriatrics, co-morbidity ...............................................................................................7
1.3. Pharmacometrix: PB-PK / PK-PD and population PK (Les 13-14) ..............................................................................13
1.3.0. Lumicitabine case (Les 13) .................................................................................................................................13
1.3.1. Model-informed drug development (Les 13) .....................................................................................................14
1.3.2. PBPK modelling (Les 14) ..........................................................................................................................19
2. PRECLINICAL RESEARCH AND DEVELOPMENT OF DRUGS ................................................................................................26
2.1. Drug design & discovery (Les 2+3) ............................................................................................................................26
2.2. Preclinical toxicology and pharmacokinetics ............................................................................................................36
2.3. Pharmaceutical development (Les 4+10) ..................................................................................................................36
Introduction (Les 4) ......................................................................................................................................................36
Preformulation: Physicochemical and Biopharmaceutical aspects (Les 4) ..................................................................37
Formulation and process development (Les 10) ..........................................................................................................39
Immediate release tablets ...........................................................................................................................................40
Tablets in oral controlled drug delivery .......................................................................................................................40
Suspensions ..................................................................................................................................................................41
Creams and ointments .................................................................................................................................................41
Gels...............................................................................................................................................................................41
Transdermal therapeutic systems (TTS) .......................................................................................................................42
Vaginal and intra uterine dosage forms .......................................................................................................................42
Parenteral dosage forms ..............................................................................................................................................42
Nano-sized drug delivery systems for drug targeting ..................................................................................................42
3. CLINICAL RESEARCH AND DRUG DEVELOPMENT .............................................................................................................46
3.1. Clinical drug development / clinical studies (Les 5-9) ...............................................................................................46
FASE 1 – VAN MENS TOT MUIS ....................................................................................................................................46
FASE IIA (IB) - FIRST INTO TARGET POPULATION .........................................................................................................52
FASE 3 – BEVESTIGEN VAN EFFICACITEIT & VEILIGHEID ..............................................................................................55
FASE 4 – POST MARKETING SURVEILLANCE .................................................................................................................61
Improvements ..............................................................................................................................................................62
Study design: hierarchy & level of evidence ................................................................................................................66
3.2. Small molecules versus biologicals (Les 16) ..............................................................................................................70
3.3. Vaccines development (Les 17) .................................................................................................................................73
4. BIOSTATISTICS, DATA PROCESSING AND REPORTING ......................................................................................................85
1
,5. EVALUATION OF THE SAFETY OF DRUGS (Les 18) ............................................................................................................85
5.1. Pharmacovigilance ....................................................................................................................................................85
6. REGULATION IN A EUROPEAN CONTEXT ..........................................................................................................................96
6.1. Guidelines and regulation in clinical research (Les 15) .............................................................................................96
6.2. Drug approval and market authorization (Les 20) ................................................................................................. 100
7. HEALTH, ECONOMY AND SOCIETY ................................................................................................................................ 106
7.1. Health care systems and reimbursement (Les 19) ................................................................................................. 106
7.2. Drugs and society (Les 21-22) ................................................................................................................................ 112
7.3 Drug Life Cycle (Les 23) ........................................................................................................................................... 122
2
,1. CLINICAL PHARMACOLOGY AND PHARMACOKINETICS
1.1. BASIC CONCEPTS (LES 1)
Drug development process
- Levencyclus van drug development process : 3 onderdelen
o Non clinical: discovery fase, vooral dieren proeven & in vitro testing (non-clinical hierdoor), synthese &
formulatie, beste design zoeken met de hoogste kwaliteit zo goedkoop mogelijk
o Clinical studies: alles wat betrekking heeft tot mensen/patiënten, testen op mensen,
▪ IND: molecule beginnen testen op mensen, investigation new drug, fase van studies (1 tot 3),
in leuven vooral fase 1 van de studie gedaan
o Post approval: ongeveer 10 jaar tot men aan deze fase komt,
▪ NDA/BLA: beslissen of het aangeboden mag worden op de markt, registratie van de nieuwe
drug NDA (=new drug application)
▪ BLA (= biological license application), patent duurt 20 jaar, men wilt alle fases die voor het
uitbrengen op de markt komen liefst zo kort mogelijk, zodat verkoopperiode zo lang mogelijk
is binnen die 20 jaar voor het patent
▪ Fase 4 studies: studies uitgevoerd na approval van GM, wanneer het rondgang doet in
populatie
Drug life cycle
- Early: tijd voor approval, in deze periode moet je geld investeren voor onderzoek & ontdekking van het GM,
tijdens development moet je dus investeren
- Middle: launch, komt op de markt, approval, verkopen van GM, hier kan je pas geld verdienen, in ideale wereld
is groene deel groter dan het rode
- Late: einde van patent, hier gaat winst vaak beginnen dalen omdat andere bedrijven ook kans krijgen tot
productie, verlies van markt exclusiviteit, generische GM, bio-similars, competitie tussen GM
3
, Biopharmaceutical innovation
1ste wave – small molecules (symptomatic)
- Screenen van groot aantal compounds
- Er zijn veel small molecules: gericht naar symptomen
- Nadeel: off-target effects/toxiciteit
- Voorbeeld: statins
o Zal enzym blokkeren waardoor cholesterol productie geremd wordt, hoge affiniteit voor target &
gewenst dat het enkel werkt tegen dit target, maar vaak ook andere targets aanwezig waardoor
toxiciteit
2de wave – biologicals (disease modifying)
- Ontworpen op basis van target; specifieker
- Gericht naar disease modifying
- Voordelen: minder off-target effects
- Voorbeeld: PCSK9 inhibitors
o -mab: gehumaniseerde monoklonale AB
o Als er toxiciteit optreedt is dit vaak door on-target effects
o Normale werking van PCSK9 in lever
▪ LDL cholesterol bindt aan LDL receptor & wordt opgenomen in hepatocyt
o Bij veel PCSK9
▪ Downregulatie van LDL receptor waardoor minder receptoren → minder cholesterol uit
systeem → hoger cholesterol in bloed
o Toedienen van monoklonale AB
▪ Zullen PCSK9 remmen waardoor meer LDL receptoren actief blijven → meer cholesterol
opgenomen & afgebroken → minder cholesterol in bloed
3de wave – generic medicine (potentially transformational)
- Proberen behandelen & genezen van ziekte, behandelen/moduleren van onderliggende oorzaak van ziekte
- ATMPs= Advanced Therapy Medicinal Products
- Voorbeeld: siRNA, gen therapie
o Gaan interfereren op niveau van gen-expressie in de cel
- Voorbeeld: cholesterol & PCSK9
o Downregulatie van PCSK9 door GalNAc-siRNA conjugaat: dit gaat interfereren met transcriptiefactor
voor PCSK9 en binding van het PCSK9 encoding mRNA met het siRNA loaded RISC complex zal leiden tot
degradatie van het PCSK9 mRNA
- Voorbeeld: SARS-CoV-2 mRNA vaccins
o Gebruiken van expressie van bepaald onderdeel van virus om toe te dienen als vaccin waardoor
antistoffen aangemaakt worden in patiënt omwille van ‘onbekende eenheid’ in het lichaam
4
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller flowerbiomed. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for $13.94. You're not tied to anything after your purchase.
