Final: AntibodyPK Flashcards
4 Applications of Antibodies
- Alteration of Toxin Disposition
- Elimination of Cells
- Alteration of Cell Function
- Drug Delivery
Example of Alteration of Toxin Disposition
Anti-Digoxin-Fab
Adalimumab or Humira [TNF-Alpha Inhibitors]
Example of AB cell elimination
Keliximab [Anti-CD4 IgG]
AB example of alteration of cell function
Abciximab [Anti-CD41] =GIIB/IIIa blocker
Example of an ADC
Gemtuzumab ozogamicin
Antibodies which are ______ undergo phagocytosis, where as anti bodies which are less than _____ undergo renal elimination.
- Phagocytosis
- Renal Elimination
______: is when a sugar residue is added to an antibody allowing it to bind to receptors on cell facilitating the breakdown of the antibody.
Receptor mediated endocytosis. [Component Specific process]
_____ is a protein which undergoes receptor mediated endocytosis with the addition of mannose to its structure to facilitate binding to its receptor.
Tissue Plasminogen Activator [TPA]
This occurs in a concentration dependent manner.
______ is a receptor which protects all antibodies. The role of this receptor is to capture internalized IgG and intercept its path to the lysosome. This function of this receptor is _____ specific.
FcRN-Gamma
pH specific = acidic environment needed.
T or F: FcRn function is saturable.
True —> Concentration dependent elimination
Target mediated disposition means that: interaction of the drug with its receptor influences _____.
Disposition
Trastuzumab is a drug which exhibits TMD, how do plasma concentration relate to the rate of clearance for this drug?
As plasma concentrations increase, plasma concentrations would decrease due to saturable TMD.
In TMD, how is dose related to Vss and CL
As you increase the dose of the drug, Vss and CL both decrease.
For drugs which undergo target mediated disposition, would the first dose or later doses under go more rapid clearance?
The first dose. This is b/c TMD is a saturable process. With this said, on the first dose we also observe higher clearances with higher doses.
Anti-Drug Antibodies are the highest risk for ____ administration.
- SQ 2. IM. IV
What types of antibodies have the highest risk of ADA?
- AB
- Chimeric
- Humanized
- Fully Human
ADA formation _____ clearance.
Increases
Antilenercept is prone to the formation of _____, which leads to a major increase in clearance of the drug.
Anti-Drug-Antibodiies
TMD saturation occurs at ____ doses, while FcRn saturation occurs at ____ doses.
1) Low
2) High
Antibody distribution by convection is dependent on ____ and ____.
1) Amount of Fluid
2) Concentration in plasma
FcRn variability influences _____, but does not influence ____.
1) Pharmacodynamics
2) PharmacokineticsRi
Rituximab variability occurs largely due to what genetic change?
Varability in FcRn—> patients with 158-Valine have a more superior response than those with a 158-phenylalanine.
This is because those with the phenylalanine have a dysfunction FcRn receptor.
Why do higher doses of methotrexate (or any immunosuppressive) increase the plasma concentration of drugs like infliximab or adalimumab?
This is because immunosuppresive drugs block the formation of anti-drug-antibodies.
In diabetic nephropathy, protein clearance _____ considerably.
decreases—> more protein is being secreted in the urine.
Bevacizumab ______ the plasma concentration of mAbs, while it ______ the concentration in the tumor.
No-effect on plasma concentration.
Decreases delivery to tumors, due to a decrease in angiogenesis and the vascularization of the tumor. This leads to a decrease in convection leading to a decrease in tumor concentration.
_____ have a high % of anti-drug antibodies
ANTI-TNF Alpha drugs.
