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Large Molecule PK
Large Molecule PK - Final Info
| Question | Answer |
|---|---|
| Name 2 areas where therapeutic proteins (ie. monoclonal Ig) are playing an increasing role? | Oncology & immune-mediated diseases |
| Therapeutic proteins have potential for ________________ in any PK process (ADME). | Nonlinearities |
| Why is mathematical moeling for therapeutic protein PK data necessary? | Required to characterize complex nonlinear PK properties |
| How is FcRn (neonate Fc receptor) useful? | It can salvage endogenous IgG or IgG-based monoclonal Ig's from degradation |
| How long is the half-life for most human/humanized monoclonal Ig's?What implications does this have for dosing? | T1/2 ~2-3 weeks - allows for LESS FREQUENT DOSING (ie. q8-12weeks)! |
| What PK parameter is affected by the degree of "human-ness" & how so? | T1/2. Increase T1/2 with increasing degree of "human-ness" ** T1/2 HIGHEST --> lowest: humanized > chimeric > murine |
| Comparability for therapeutic proteins depends on a combination of what 3 factors? | - Biochemical, biological, & PK comparabilities |
| What immune/physiologic reaction is likely to occur upon administration of a protein 'antigen'? | Antibody formation due to to its "foreign" nature |
| Name 2 outcomes that may occur if an unwanted immune response (immunogenicity) does occur? | Loss of efficacy and/or severe SE (woof!) |
| Contrast metabolism between small & large molecules. | -Small: generally by CYP450 and/or renally excreted *Large: elim by specific & non-specific pathways - Non-specific ex: FcRn-med recycling, proteolysis, Fc(g)R-intxn - Specific ex: TMDD (target-med-drug disposition) pathway |
| By what mechanism could certain disease states cause a possible drug-disease interaction with a large molecule? | Pro-Inflammatory diseases (inflam, infection, RA) can cause higher CYTOKINE levels (ie. IL-6, TNF-a, INF-(g), IL-1(b)) --> DOWN REGULATION of CYP450 enz involved in metabolism |
| What could be used to resolve a drug-disease interaction with a large molecule? | Therapeutic proteins (ie. mAbs) that target certain cytokines (ie. IL-6) can REVERSE the cytokine-induced CYP450 depression! |
| What is the predicted % of large molecule medicines that will be approved within the next couple of years? | > 50%! |
| Brand:Generic as Biological meds:_________________ (term) | Bio-similar |
| Name a HUGE advantage (esp for patients) of bio-similar production | COST! Currently, most pt's cannot afford due to such a high cost. Bio-similars can be produced at a considerably lower cost allowing MARKET EXPANSION & LOWER HEALTHCARE COSTS |
| The general consensus among analysts attribute ____% cost reduction due to bio-similars (vs. innovator products) | 25-35% - so pretty darn significant! |
| Name 4 intrinsic factors that affect therapeutic protein CL. | - Affinity to FcRn - Anti-Drug Antibody formation - Proteolytic degradation - Receptor binding & internalization |
Created by:
myassen
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