Antibody PK

Question 1

mAb approved for use

Answer 1

> 75

Question 2

polyclonal Abs vs monoclonal Abs

Answer 2

poly: immunization leads to production of multiple genetically specific AB-producing cells with a range of affinity and specificity
mono: large quantity of abs produced all of the same kind

Question 3

Abs use: immunotoxicotherapy
intent
ex

Answer 3

complete neutralization of toxin/xenobiotic
digoxin immune Fab
adalimumab, bevacizumab, infliximab, alirocumab

Question 4

abs uses list

Answer 4

immunotoxicotherapy
elimination of cells
alteration of cell function
drug delivery

Question 5

abs use: elimination of cells
ex
moa

Answer 5

anti-CD4 IgG
kaliximab
antibody mediated clearance via opsonization and marking for clearance

Question 6

abs use: alteration of cell function
ex
moa
use

Answer 6

alters cell function/signaling

abciximab (antiCD421) prevents plt aggregation
indicated for acute MI, MI proph, UA

Question 7

abs use: drug delivery
ex
moa

Answer 7

increasing the efficiency of drug delivery to desired sites
ex) gemtuzumab ozogamicin
ozo-Ab complex binds tumor cell surface toxin and induces cell death

Question 8

Ab pk general expectations

Answer 8

good abs w SQ or IM (F 0.5-1)
biexponential disposition
long terminal halflife
small Vd

Question 9

mechanisms of elimination for peptides and proteins

Answer 9

fluid phase endocytosis and catabolism
renal filt
phagocytosis
component specific - receptor mediated endocytosis
component specific receptor mediated protection
drug specific receptor mediated endocytosis

Question 10

fluid-phase endocytosis and proteolysis
specific or non?
pathway

Answer 10

NON SPECIFIC

porteins/peptides —> amino acids in lysosomes–> degradation

Question 11

renal filtration/phagocytosis and proteolysis
_____ - specific
phagocytosis when ?
proteolysis when?
MW effect on GSC (glomerular sieving coefficient)

Answer 11

size-specific
<50kDa = renal filt and proteolysis
>400kDa = phagocytosis

dec MW inc GSC

Question 12

GSC and estimating renal CL

Answer 12

GSC underestimates renal CL

Question 13

receptor-mediated endocytosis and catabolism
two types?
ex?

Answer 13

component specific uptake receptors (t-PA)
component specific protection receptors (FcRn)
hepatocytes, RES, kupfer cells, liver, fibroblasts, macrophages
t-PA
FcRn- binds IgG and returns it to cell surface; the reason why IgG CL is so low!

Question 14

t-PA and receptor mediated endocytosis and catabolism
how is CL so high?
what is t-PA clearance similar to?

Answer 14

rapid elim is bc of mannos and mannos receptors
dec mannos receptors, dec CL, inc Cp
t-PA clearence rate is ~liver BF

Question 15

FcRn aka?
info
elim?

Answer 15

the Brambell receptor
saturable, transient absorption in neonates
saturable meternofetal transfer
very long plasma half life
concentration-dep elim

elim is non linear

Question 16

target mediated disposition
Vss _____ with increased dose
linear or nonlinear, why?
CL ____ w inc dose

Answer 16

Vss dec with inc dose
CL dec w inc dose
nonlinear, because even though you are giving the same maintenance dose, the antibody target is wiped out more and more with each dose so theres less target-mediated elim–> inc AUC and dec CL with time

Question 17

ADA

Answer 17

anti-drug antibodies
greatest in rodent ab>chimeric>humanized>fully human
SQ>IM>IV
results in rapid elim of drug :/

Question 18

for fluid phase endocytosis, phagocytosis, renal filt, catabolism
and drug-specific and component specific processes, elim is ___-dependent

Answer 18

dose dependent