-
Half life with SC injection vs IV
sub Q half life is much longer (10 hrs vs 68 min)
-
Diffusion of peptides and proteins across capillary endothelial cells is determined by
- size
- shape
- charge
- structural and chemical characteristics of capillaries
-
Elimination of proteins from the blood
- cytokines taken up by the liver and filtered by the kidney
- peptidases and proteases eliminate protein drugs
-
three types of capillary endothelia
- discontinuous
- fenestrated
- continuous
-
discontinuous endothelia
- liver, spleen and bone marrow
- frequent large gaps >100 nm
- no endothelial cells or basement membrane
-
fenestrated capillary endothelia
- glomeruli, intestines, tissues with rapid fluid movement
- 60-80 nm opening between cells
- heparin laden membrane
- devoid of lipid
-
continuous endothelia
- majority of capillary surface area
- no gaps and few fenestrations
- brain, lung, muscle, connective tissue
- no gaps in brain (BBB)
-
Cell types of the liver
- hepatocytes (78%)
- endothelial cells (3%)
- kupffer cells (2%)
- fat storing cells (1.5%)
- sinusoids (11%)
- space of disse (5%)
- Bilary tree (0.5%)
-
two processes of uptake
- receptor mediated endocytosis
- nonselecive pinocytosis
-
Up to ___% of proteins and peptides in the plasma with molecular weights less than 25KD are cleared in a single pass unless protein bound
50%
-
The glomerulus is ____ charged
negatively
-
Peptides and small proteins (less than ____kd) pass into the ultrafiltrate almost like inulin.
5kd
-
protein/inulin clearance ratio
- rangest from 0 to 1
- 1= small peptides
- 0=albumin
-
glomerular sieving coefficient
- 0=albumin
- 0.5 anions
- 0.8 cations and 20kd
-
proteins not found in the urine are metabolized by___ if low molecular weight
brush border enzymes
-
proteins not found in urine are metabolised by ____ if high MW
lyzosymes after endocytosis
-
macromolecules bound to proteins to increase plasma half life
- dextran
- peg
- polystyrenemaleic acid copolymer
- albumin
- monoclonal antibodies
-
an example of conjugating proteins and macromolecules
- l asparaginase
- enzyme with anti tumor effects
- bound to PEG to reduce anaphylactic reactions and increase half life in the plasma
-
Pegylation of proteins and peptides
- covalent binding of PEG to proteins or peptides
- increase stability
- increases water solubility
- increases MW
|
|