Erythropoietin PKPD

Question 1

Erythropoietin

Answer 1

hormone that regulates production of red blood cells and hemoglobin
-when oxygen pressure goes down, the kidneys produce more erythropoietin, which then stimulates more bone marrow cells, and more bone marrow cells will produce more red blood cells, more hemoglobin means more oxygen
oxygen goes down, hemoglobin goes up and vice versa
-glycoprotein

Question 2

Indications

Answer 2

• CRF (chronic renal failure)
• Cancer
• AIDS
• Prematurity
• Autologous transfusion

Question 3

AE

Answer 3

• HTN
• Iron deficiency
• Pure red cell aplasia (rare)
• Increased survival of cancer cells (large doses)

Question 4

Erythropoiesis stimulating agents

Answer 4

-Epoetin, Biosimilar EPOs, Darbepoetin alfa, CERA, SEP, EPO fusion proteins

Question 5

PK model

Answer 5

• zero order rate constant for absorption from the SQ site to blood
• F after SQ dosing
• Fraction of bioavailable dose which is absorbed via the first-order component
• First order rate constant for absorption of EPO from the SQ site to blood

Question 6

PK model: modifications

Answer 6

• linear and nonlinear Cl
• endogenous EPO: circadian rhythm
• Peripheral distribution
• Continuous first-order absorption from SC site
• Saturable F vs. dose relationship

Question 7

Absorption

Answer 7

tmax: 5-30 h
- flip flop kinetics: half life 24-79 h (absorption is slower than elimination)
- glycosylation or pegylation of EPO molecule inc absorption times
- dose dependent F (F inc with dose)

Question 8

Distribution

Answer 8

• within the plasma
• Vd: 40-60 mL/kg
• limited extravascular distribution

Question 9

Elimination

Answer 9

• 2 Cl pathways:
  
  • EPOR mediated endocytosis (cleared by binding to receptor)
  • EPOR independent linear Cl
• Dose dependent half life after IV injection = 8 h
• Kidney, liver, lymph exert negligible effect on EPO Cl
• Cl mediated through receptors

Question 10

EPO Cl after stem cell transplantation

Answer 10

Cl decreased