Antibody PK

Question 1

Polyclonal IgG Antibodies

Answer 1

-Need an animal to produce them

Question 2

Immunotoxicotherapy

Answer 2

• Use of an antibody to neutralize a soluble toxin or xenobiotic
• dec conc of soluble substance which sometimes affects its CL and its vd and prevents it from binding to receptor
• ex: digibyte, the digoxin immuno fab therapy for reversal of digoxin intoxication

Question 3

Elimination of cells

Answer 3

• coat cell with antibody and market for destruction by cells of the immune system
  ex. ) rituximab

Question 4

Alteration of cell function

Answer 4

Abciximab causes inhibition of PLT aggregation, clotting; indicated for acute MI, MI prophylaxis, unstable angina

Question 5

Drug delivery

Answer 5

Use of antibodies to delivery toxins to desired cells in the body
-Ozogamicin is the toxin gemtuzumab uses

Question 6

Antibody PK

Answer 6

• good absorption following SQ or IM dosing (F: 0.5-1)
• bi-exponential disposition with long terminal half life (20 d) and low rates of cl
• small vd (3-9L)

Question 7

fluid-phase endocytosis and proteolysis

Answer 7

• non specific
• proteins/peptides broken down to component amino acids
• degradation products are not likely to be toxic
• dominant pathway when other ones aren’t available

Question 8

Renal filtration

Answer 8

• size specific mechanism of elimination
• phagocytosis may be primary mechanism of elimination for proteins and aggregates
• renal filtration and proteolysis is for small molecules

Question 9

Targeted mediated disposition

Answer 9

• Vss decreases from non-compartmental analyses
• CLd decreases with increasing dose
• Cl decreases with dose when receptor binding leads to drug elimination

Question 10

FcRn

Answer 10

• the brambell receptor
• transient, saturable GI absorption in neonates
• saturable maternofetal transfer
• long half life
• concentration dependent elimination
• heterodimer
• pH dependent affinity
• protects IgG antibodies from intracellular catabolism
• high affinity for IgG at high pH (9-10)

Question 11

FcyRs

Answer 11

-may contribute to the elimination of circulating antibodies

Question 12

IVIG

Answer 12

• pretreatment leads to a dose dependent inc in APAb Cl
• the PK effect is not observed in FcRn knockout mice, suggesting that this effect is mediated via competition for FcRn
• PKPD modeling indicates that saturation of FcRn accounts for 50% of the therapeutic benefit provided by IVIG in rat and mouse models of ITP

Question 13

Anti-drug antibodies

Answer 13

• Protein drugs often induce the development of an immune response, leading to the production of anti-drug antibodies (ADA) within the host
• For mAb, risk for ADA appears to be greatest for rodent antibodies>chimeric>humanized>fully human
• risk is related to ROA with SQ>IM>IV
• ADA typically lead to a rapid inc in the elimination of the drug