Measurement of Drug Absorption

Question 1

Define bioavailability

Answer 1

• The extent and rate of absorption of a drug OR
• the amount of drug reaching systemic circulation that is able to have an effect
• determined by analyzing pharmacokinetics by measure plasma drug concentration

Question 2

how is absolute bioavailability calculated

Answer 2

F = AUC oral/AUC IV x Dose iv/Dose oral

Question 3

extent of absorption is more important for drugs with non-linear or linear pk

Answer 3

linear

Question 4

how is extent of absorption measured?

Answer 4

• total AUC under plasma level vs. time curve
• e.g. F x D = Cl x AUC_0->infinity OR
  
  • FD = Cl x (AUC_0-t+ C_t/ß) where
    
    • F = fraction of dose administered which is absorbed
    • ß = rate constant of terminal elimination phase
      
      • for one compartment model this =K (the loss rate constant)

Question 5

Absolute bioavailability compares

Answer 5

• the bioavailability of the active drug in systemic circulation following non-intravenous administration with the bioavailability of the same drug following intravenous administration.
• often obtained in a cross over study

Question 6

the comparison of AUC of a test product to a standard product is

Answer 6

relative bioavailability

Question 7

what is the most common method used to calculate AUC

Answer 7

linear trapezoidal rule

Question 8

the larger the number of trapezoids, the less or more accurate the AUC

Answer 8

more accurate

Question 9

describe the trapezoidal method

Answer 9

• the area under the plasma concentration time curve is divided into trapezoids
• the area of each trapezoid is added to obtain cumulative AUC

Question 10

how is the area of the trapezoid calculated?

Answer 10

• Area = 1/2 (c + d) (t2-t1)
  
  • where c is plasma cocentration at the first timepoint and d is the plasma conc at the next timepoint
  • t2-t1 = the time interval for the trapezoid
• the last trapezoid is calculated by
  
  • Area = Cp(last concentration)/k
    
    • where K is the slope

Question 11

Differences in the shape of profiles with same AUC are a result of differences in the

Answer 11

Rate of absorption

Question 12

differences in the rate of absorption between products may be shown by comparing

Answer 12

the mean peak plasma concentration (Cpk) or the mean time to peak (tpk) fore each product and showing significanct difference between them

Question 13

True or False: more rapidly absorbing products have higher Cpk and shorter tpk

Answer 13

True

Question 14

When is the Wagner Nelson model is used to measure absorption profiles for drugs that obey one or two compartment models?

Answer 14

for drugs that obey one compartment open model

Question 15

True or False: the AUC method for measurign extent of absorption is accruate for drugs obeying any linear multicompartment model

Answer 15

True

Question 16

the absorption phase is described by single or multiple exponential equations?

Answer 16

Single

Question 17

what is Cpk

Answer 17

mean peak plasma concentration

Question 18

what is tpk

Answer 18

mean time to peak concentration

Question 19

what is required to estimate Cpk and tpk

Answer 19

a continuous concentration vs. time profile

Question 20

absorption profile at any time following administration of a drug (At) is calculated by these two equations

Answer 20

At = Ab + Ae

where Ab = amount in body

Ae = amount eliminated

Or

At = VCp + VK (K_{0 to infinity)} Cp Dt

Question 21

what is needed to be known to estimate At

Answer 21

Volume of Distribution (V) and K (rate constant)