Introduction to biologics Flashcards
What is a biologic?
Any medicinal product derived from a living organism.
I.e. Insulin and human growth hormone
What are first-generation biologics?
Replicas of human hormones
They are produced by transfecting human gene into a cell line that produces the biologic protein
What are second-generation biologics?
‘Engineered’ proteins
Gene altered to change the structure of the biologic protein
What are third-generation biologics?
Large molecules designed for a specific biological process.
How are biologics produced?
Manufactured using a living cell line, a highly complex process that is difficult to replicate.
It makes the production of generic copies (biosimilars) challenging.
What is an antibody?
Large protein components of the immune system.
They bind to a pathogen (antigen)
It flag’s pathogens for destruction by immune cells
or Directly inhibits the pathogen through interaction
What is a monoclonal antibody?
Lab-produced antibody to mimic the natural antibodies
What are fusion proteins? (Chimeric proteins)
Proteins created through the joining of two or more genes that originally coded for separate proteins.
What are the nomenclatures of adalimumab? -mab -u- -lim- Ada-
-mab = monoclonal antibody
-u = fully human molecule
-lim = indicates the target is the immune system
Ada - chosen by the manufacturer
What is Adalimumab?
A monoclonal antibody that inhibits TNF-alpha, an inflammatory cytokine produced by the human immune system.
What are the nomenclatures of monoclonal antibodies? (Third segment)
- o-
- u-
- xi-
- z-
Third segment indicates the source:
- o- mouse
- u- human
- xi- chimeric (human and mouse)
- z- humanized (95% human)
What are the nomenclatures of fusion proteins? (Stem)
- mab
- mib
- nib
- tnib
- cept
stem (last segment):
- mab = monoclonal antibody
- mib = protease/proteasome inhibitors
- nib = small molecule inhibitor
- ‘tinib’ indicates tyrosine kinase inhibitor, ‘anib’ indicates angiogensis inhibitor
- cept = receptor molecules
What is Insulin biologic used for?
Diabetes mellitis (type 1), a disease characterises by failure of insulin production and high serum glucose concentration.
What is the half life of adalimumab that is administered subcuateneously?
2 weeks
What is the difference in drug interactions for biologics and small molecule drugs?
Biologics = rare drug interactions
small molecule drugs = common drug interactions
what is the difference in molecular weight for biologics and small molecule drugs?
Biologics = High molecular weight
Small molecule drugs = Low molecular weight
what is the difference in PK and PD properties for biologics and small molecule drugs?
Biologics = Complex PD, linked to PD
Small molecule drugs = Predictable PK, distinct from PD
what is the difference in production of biologics and small molecule drugs?
Biologics = produced using biological processes
Small molecule drugs = chemical production
what is the difference in selectivity between biologics and small molecule drugs?
Biologics = Highly selective for target
Small molecule drugs = less selective
what is the difference in distribution between biologics and small molecule drugs?
Biologics = limited distribution
Small molecule drugs = distribution varies between molecules
What is the difference in absorption between small molecule drugs and large biological molecules?
Small molecules = rapid absorption
Large biological molecules = shallow increase, long half-life; sustained conc. of the drug in the body
How are biologics admininstered?
Subcutaneously, intravenously, intramuscularly
There are no commercially available orall routes
Explain features of absorption of biologics.
Major route of absorption for biologics is lymphatics
-large molecular size precludes capillary absorption
Tmax is reached after days
List key features of volume of distribution for biologics
small volume of distribution
2-4L for monoclonal antibodies
Transport to tissues is an active process
List key features of elimination for biologics and small molecule drugs
small molecule drugs are commonly eliminated via hepatic metabolism steps or excretion in urine/bile
Biologics undergo:
Endocytosis - drug taken into the cell and removed from circulation
Proteolysis - antibody mediated clearance. protein is broken down into smaller polypeptides
Target-mediated clearance (decreases with saturation of target) - elimination of monoclonal antibodies through antigen specifc interactions
Formation of immune complex
What are the nomenclatures of monoclonal antibodies? (Second segment)
- bac-
- lim-
- tum-
Second segment indicates the target:
- bac- bacteria
- lim- immune system
- tum- tumour
