L45 - Extravascular Administration 1

Question 1

What is extravascular administration?

Answer 1

Administration by any other route than the intravenous route
// subcutaneous, intramuscular, oral

Question 2

Why are oral dosage forms taken?

Answer 2

For a systemic effect in the body after absorption

Question 3

Why is oral dosage form the preferred route of administration?

Answer 3

• GI tract designed for absorption
• easier, no infection risks
• broad range of oral dosage forms // liquids, powders and granules, tablets, capsules
• could incorporate dif mechs for drug release and provide immediate/delyaed/extended/controlled drug delivery

Question 4

What is the passage of drugs from absorption site to systemic site?

Answer 4

• passive absorption (ficks law)
• active absorption by transporters (michaelis menten kinetics)
• (first order process)

Question 5

What is eqn to calculate the amount of drug remaining at the absorption site?

Answer 5

X = X0 x e^-ka.t
Ka - rate constant for the drug absorption

Question 6

What is ka?

Answer 6

• rate constant for the drug absorption
• proportional to the amount of drug present at the absorption site

Question 7

What is the one compartment model?

Answer 7

• simplest model
• most frequently used (dispite simplification and assumptions)
• drug rapidly distributes into a homogenous fluid volume in the body

Question 8

What are assumptions for the one compartment model for extravascular administration?

Answer 8

• elimination - first order process (k rate constant)
• absorption - first order process (ka rate constant)
• linear kinetics - no enzymes or transporters involved in ADME process are saturated

Question 9

What is the variation of A the amount of drug in the body with time eqn?

Answer 9

dA/dt = kaxX - kxA
Rate of change of drug in body = rate absorption - rate elimination

Question 10

What is the integration of eqn1 using C=A/V?

Answer 10

C = B x e^-kt - B x e^-kat

Question 11

What is B?

Answer 11

Constant
B = kaxFxD / V(ka-k)
F - bioavailability
D - dose
C - druc conc at t
V - volume distribution
K - elim rate const
Ka - abs rate const

Question 12

What is eqn1 profile like at t=0?

Answer 12

• all drug is at absorption site and none in body
• rate absorption max X0 = dose
• rate elim is zero A=0

Question 13

What is the absorption like in the absorption phase of eqn1 profile?

Answer 13

• as more drug asborbed
• rate of absorption declines
• rate of elim increases
• drug conc increases in plasma until Cmax reached at tmax
• kaxX >kxA

Question 14

What is the peak like at eqn1 profile?

Answer 14

• at tmax
• elim rate has increased
• absorption rate has decreased
• kaxX =kxA

Question 15

How is tmax calculated from the eqn1 profile?

Answer 15

Tmax = ln(ka/k) / ka - k
Tmax = 2.303log(ka/k) / ka - k

Question 16

What is tmax like?

Answer 16

• depends on k and ka
• dose independent
• ka has bigger effect on tmax than k
• increases when ka decreases // faster absorption means shorter time to get to Cmax

Question 17

How can you predict Cmax in eqn1 profile?

Answer 17

Cmax = B x e^-ktmax - B x e^-katmax

Question 18

What is Cmax dependent on?

Answer 18

• dose, D
• fraction absorbed, F
• vol distribution, V

Question 19

What is the elimination phase like in eqn1 profile?

Answer 19

• amount of drug in body and elim rate has increased
• amount of drug at absorption site and absorption rate has decreased, becomes 0 once all absorbed
• kaxX < kxA
• amount of drug in body and plasma conc decreases