Kinetics: Lecture 7: Kinetics Of Oral Absorption

Front 1

Anatomical and physiological factors involved in the model of absorption from extravascular sites includes what?

Back 1

Includes factors such as GI motility, and surface area for absorption.

Front 2

Give an example of how the dosage form used can effect absorption?

Back 2

For example, a solid needs to first disintegrate, then dissolve in GI fluids before absorption is possible.

Front 3

Give some examples of the physicochemical properties of a drug?

Back 3

Lipid solubility, size, etc.

Front 4

For oral absorption the rate of drug build-up in the body is equivalent to what?

Back 4

It is the rate of drug absorption minus the rate of drug elimination.

dDb/dt = dDgi/dt - dDe/dt

Front 5

What does Dgi equal?

Back 5

Dgi is the amount of drug in the gastrointestinal tract.

Front 6

What does De equal?

Back 6

The amount of drug eliminated.

Front 7

What three phases can be identified from the PLASMA DRUG LEVEL-TIME curve?

Back 7

1. The absorption phase

2. post-absorption phase

3. elimination phase

Front 8

In a plasma drug concentration verses time curve what is equal at the peak concentration?

Back 8

At peak concentration:

Rate of absorption = rate of elimination

[dDgi/dt] = [dDe/dt]

Front 9

In a Cp against t curve for oral absorption what is the relationship between the rate of absorption and rate of elimination during the post-absorption phase?

Back 9

During the post-absorption phase the rate of absorption is less than the rate of elimination.

Front 10

During the absorption phase what is the relationship between the rate of absorption verses the rate of elimination?

Back 10

During the absorption phase the rate of absorption is greater than the rate of elimination.

Front 11

During the elimination phase what is the rate of absorption equal to?

Back 11

During the elimination phase the rate of absorption is 0.

Front 12

What is Ka?

Back 12

Ka is the first-order rate constant for absorption.

Front 13

What do K and Ka make it possible to determine?

Back 13

They make it possible to determine peak and trough plasma concentrations during multiple dosing.

Front 14

If Ka increases at a steady K how does it affect the Cmax, tmax, and AUC?

Back 14

1. Cmax increases

2. tmax decreases

3. AUC remains the same

Front 15

If k increases at a steady Ka how does it affect the Cmax, tmax, and AUC?

Back 15

Cmax, tmax, and AUC all decrease

Front 16

The parameters Ka, K, and tmax are useful in determining what?

Back 16

They are useful in determining the bioequivalence of chemically equivalent products.

Front 17

The selection of a ? and ? is typically based on the data gathered.

Back 17

The selection of a model and order is typically based on the data gathered.

Front 18

When does a Zero-order absorption process occur?

Back 18

It occurs when the process is saturable or when a controlled-release system is used.

Front 19

The Wagner-Nelson Method assumes a ? model.

Back 19

The wagner-nelson method assumes a one-compartment model.

Front 20

What is Du representative of in the Wagner-Nelson Method?

Back 20

Du is the amount of unchanged drug in the urine.

Front 21

In Wagner-Nelson Method why is only the initial segment of the curve used?

Back 21

Because the terminal part tends to be non-linear (as absorption nears 100%, it becomes difficult to accurately assay Cp)

Front 22

Only ? ? samples will yield accurate pharmacokinetic parameters.

Back 22

Only valid urine samples will yield accurate pharmacokinetic parameters.

Front 23

What does De represent?

Back 23

De is the total amount of drug eliminated (parent and metabolites).

Front 24

In a one-compt model what does Db equal?

Back 24

Db = VdCp

Front 25

The loo-riegelman method assumes what? What is required to determine all the parameters needed?

Back 25

It assumes a two-compt model. The drug needs to be given both po and iv in order to determine all the parameters needed.

Front 26

In the loo-riegelman method what does Dp, Dt, and Du refer to respectively?

Back 26

1. Dp = amt of drug in the central compt

2. Dt = amt of drug in the tissue compt.

3. Du = amt of drug eliminated by all routes

Front 27

When using the feathering technique does k or ka represent the steeper slope?

Back 27

ka represents the steeper slope.

Front 28

When can a reversal of the values for the rate constants ka and k occur?

Back 28

A reversal of the values for these can occur when they are estimated from oral absorption data. This occurs for drugs with very fast elimination (k>ka).

Reversal occurs for some drugs with k>.69/hr such as isoproterenol and salicyluric acid.

It could also occur for an extended release product if ka drops well below k.

Front 29

In order to be sure that Ka>K (as would be indicated by oral data) the drug must be given to the same patient how?

Back 29

In order to be sure that Ka > k the drug must be given to the same patient intravenously.

Front 30

A drug with a high value for k, which means it has a ? half-life, is probably not suitable for what?

Back 30

A drug with a high value for k, which means it has a short half-life is probably not suitable for oral administration.

Front 31

What may create a lag time in some individuals?

Back 31

Factors such as stomach emptying time and intestinal motility create a lag time in some individuals. This is a delay in absorption.

Front 32

Absorption begins at the end of ?. What does onset time represent?

Back 32

Absorption begins at the end of lag time (t0). Onset time, on the other hand, represents the time needed for drug levels to attain the minimum effective concentration.