Final: AntibodyPK

Question 1

4 Applications of Antibodies

Answer 1

1. Alteration of Toxin Disposition
2. Elimination of Cells
3. Alteration of Cell Function
4. Drug Delivery

Question 2

Example of Alteration of Toxin Disposition

Answer 2

Anti-Digoxin-Fab
Adalimumab or Humira [TNF-Alpha Inhibitors]

Question 3

Example of AB cell elimination

Answer 3

Keliximab [Anti-CD4 IgG]

Question 4

AB example of alteration of cell function

Answer 4

Abciximab [Anti-CD41] =GIIB/IIIa blocker

Question 5

Example of an ADC

Answer 5

Gemtuzumab ozogamicin

Question 6

Antibodies which are ______ undergo phagocytosis, where as anti bodies which are less than _____ undergo renal elimination.

Answer 6

1. Phagocytosis
2. Renal Elimination

Question 7

______: is when a sugar residue is added to an antibody allowing it to bind to receptors on cell facilitating the breakdown of the antibody.

Answer 7

Receptor mediated endocytosis. [Component Specific process]

Question 8

_____ is a protein which undergoes receptor mediated endocytosis with the addition of mannose to its structure to facilitate binding to its receptor.

Answer 8

Tissue Plasminogen Activator [TPA]
This occurs in a concentration dependent manner.

Question 9

______ 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.

Answer 9

FcRN-Gamma

pH specific = acidic environment needed.

Question 10

T or F: FcRn function is saturable.

Answer 10

True —> Concentration dependent elimination

Question 11

Target mediated disposition means that: interaction of the drug with its receptor influences _____.

Answer 11

Disposition

Question 12

Trastuzumab is a drug which exhibits TMD, how do plasma concentration relate to the rate of clearance for this drug?

Answer 12

As plasma concentrations increase, plasma concentrations would decrease due to saturable TMD.

Question 13

In TMD, how is dose related to Vss and CL

Answer 13

As you increase the dose of the drug, Vss and CL both decrease.

Question 14

For drugs which undergo target mediated disposition, would the first dose or later doses under go more rapid clearance?

Answer 14

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.

Question 15

Anti-Drug Antibodies are the highest risk for ____ administration.

Answer 15

1. SQ 2. IM. IV

Question 16

What types of antibodies have the highest risk of ADA?

Answer 16

1. AB
2. Chimeric
3. Humanized
4. Fully Human

Question 17

ADA formation _____ clearance.

Answer 17

Increases

Question 18

Antilenercept is prone to the formation of _____, which leads to a major increase in clearance of the drug.

Answer 18

Anti-Drug-Antibodiies

Question 19

TMD saturation occurs at ____ doses, while FcRn saturation occurs at ____ doses.

Answer 19

1) Low
2) High

Question 20

Antibody distribution by convection is dependent on ____ and ____.

Answer 20

1) Amount of Fluid
2) Concentration in plasma

Question 21

FcRn variability influences _____, but does not influence ____.

Answer 21

1) Pharmacodynamics
2) PharmacokineticsRi

Question 22

Rituximab variability occurs largely due to what genetic change?

Answer 22

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.

Question 23

Why do higher doses of methotrexate (or any immunosuppressive) increase the plasma concentration of drugs like infliximab or adalimumab?

Answer 23

This is because immunosuppresive drugs block the formation of anti-drug-antibodies.

Question 24

In diabetic nephropathy, protein clearance _____ considerably.

Answer 24

decreases—> more protein is being secreted in the urine.

Question 25

Bevacizumab ______ the plasma concentration of mAbs, while it ______ the concentration in the tumor.

Answer 25

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.

Question 26

_____ have a high % of anti-drug antibodies

Answer 26

ANTI-TNF Alpha drugs.