Oral Administration

Question 1

First Order Administration Model

Answer 1

Ka - Rate of absorption (h^(-1))
K - rate of elimination (h^(-1))
X - Drug in body or in blood
Xa - Drug absorbable drug at action site

Question 2

First Order Administration Rate Equations

Answer 2

dXa/dt = -Ka * Xa

dX/dt = KaXa - KX

Question 3

Amount of drug @ time t…

Answer 3

X = [(ka * Dose)/V(ka-K)] * (e^(-Kt) - e^(-kat))

Question 4

Concentration Equation

Answer 4

C = same equation of amount of drug at time t but F (bioavailability) is included (ka * F * Dose)

Question 5

Extrapolation of…

Answer 5

Linear elimination phase (lnC v.s. time):
y-intercept: Ka * F * Dose/(V * (ka-K))
slope: -K

Absorption phase (lnC v.s. time):
slope: -Ka

Question 6

Lag Time

Answer 6

• Theoretically, intercepts of absorption and elimination lines should be equal, this rarely happens
• Actual intersection = lag times
• Indicates that absorption doesn’t start immediately after drug administration

Question 7

Reasons for Delayed Absorption

Answer 7

1. Slow tablet disintegration
2. Slow and/or poor drug dissolution from dosage form
3. Aggregation of drug particles reducing SA
4. A delayed release formulation

Usually formulation problems

Question 8

Physiology Problems with Absorption

Answer 8

1. Slow gastric emptying time

2. Dosage form taken with food

Question 9

Negative Lag Time

Answer 9

• Absorption didn’t start before drug was administered
• Usually indicates that absorption and elimination rate constants are very similar
• More complex math models are employed to provide an accurate estimation of absorption rate constant

Question 10

PK Parameters -Absorption

Answer 10

• Absorption rate constant (Ka)
• Relates overall rate of systemic drug absorption from an orally administration dosage form
• May include many rate limiting processes - disintegration, dissolution, gastric emptying, etc.
• May be zero (sustained release) or first order (immediate release, delayed release w=once release starts)
• If ka is altered, AUC = same but the curve shape is different

Question 11

PK Parameters - tmax

Answer 11

-Function of K and ka, NOT dose

tmax = [ln(ka/K)/(ka-K)] when dC/dt = 0

Question 12

PK Parameters - Cmax

Answer 12

Cmax = [F * Dose/V] * e^(-Ktmax)