Mfabs
The high cost of mAbs also prevents it from being a more common therapeutic method for treating maladies. These costs can be attributed to the multiple large doses that must be administered intravenously at regular intervals in order to maintain systemic volumes of distribution. Therefore, it is beneficial to explore an alternative method of delivery that can sustain delivery of mAbs in its therapeutic window for long periods of time.
Oral antibody dosing shows almost zero bioavailability. Intravenous administration of mAbs exhibits complex pharmacokinietics.
Subcutaneous (SC) injection of mAbs
Dangers of IV injection include non-specific toxicities, prolonged half-life, and high water solubility.
The advantage of using subcutaneous injection …show more content…
As you can see from this diagram…any free IgG that isn’t bound to FcRn is then lysed inside the cell and eliminated from the body.
Assessing the role of FcRn
There are two approaches for testing binding:
1) Create a situation where you don’t have anything to bind to. One can do this with knockout animals. However, knockout animals can be very expensive.
Why not do knockouts?
2) One can do it the other way around. One can put something else in the system that will compete with binding.
Therefore, the second paper administered non-specific IgG to compete with Rituximab.
PK model of FcRn paper
In order to test the hypothesis that FcRn is responsible for protecting Rituximab from degrading and is responsible for absorption, Ritixumab and 500mg/kg of non-specific IgG were co-administered at the subcutaneous injection site. The dose is then transferred to an absorption site by a first order process via k,inj. At the absorption site, free antibody can bind to a receptor to form a complex (DR), which is assumed to occur rapidly characterized by the equilibrium dissociation constant Kd.
Role of FcRn …show more content…
Other advantages include improved control over release kinetics.
When manipulating controlled-release systems, one must understand site-specific antibody release, correlated target-site concentrations, systemic concentrations, and clearance or metabolism.
Controlled release of mAbs
Figure 4, Paper 2
Oral antibody dosing shows almost zero bioavailability. Intravenous administration of mAbs exhibits complex pharmacokinietics.
Subcutaneous (SC) injection of mAbs
Dangers of IV injection include non-specific toxicities, prolonged half-life, and high water solubility.
The advantage of using subcutaneous injection …show more content…
As you can see from this diagram…any free IgG that isn’t bound to FcRn is then lysed inside the cell and eliminated from the body.
Assessing the role of FcRn
There are two approaches for testing binding:
1) Create a situation where you don’t have anything to bind to. One can do this with knockout animals. However, knockout animals can be very expensive.
Why not do knockouts?
2) One can do it the other way around. One can put something else in the system that will compete with binding.
Therefore, the second paper administered non-specific IgG to compete with Rituximab.
PK model of FcRn paper
In order to test the hypothesis that FcRn is responsible for protecting Rituximab from degrading and is responsible for absorption, Ritixumab and 500mg/kg of non-specific IgG were co-administered at the subcutaneous injection site. The dose is then transferred to an absorption site by a first order process via k,inj. At the absorption site, free antibody can bind to a receptor to form a complex (DR), which is assumed to occur rapidly characterized by the equilibrium dissociation constant Kd.
Role of FcRn …show more content…
Other advantages include improved control over release kinetics.
When manipulating controlled-release systems, one must understand site-specific antibody release, correlated target-site concentrations, systemic concentrations, and clearance or metabolism.
Controlled release of mAbs
Figure 4, Paper 2