Kinetics: Lecture 8: Multiple Dose Regimens

Front 1

In multiple dosage regimens it is assumed that a drug is eliminated by what process?

Back 1

It is eliminated by a first-order process and that early doses have no effect on the kinetics of later doses. The kinetics of later doses are only superimposed on earlier ones.

Front 2

Based on the principal of superimposition, the concentration-time curve in a multiple dosing case can be predicted from what?

Back 2

It can be predicted from the concentration-time data of a single-dose administration.

Front 3

If a constant dose is given at constant time periods, the plasma concentrations after each dose consists of what? So, for each time point what is the predicted plasma concentration?

Back 3

If a constant dose is given at constant time periods, the plasma conc. after each dose consist of the same data obtained after the single dose. For each time point, then, the predicted plasma concentration is the sum of the residual concentration resulting from each previous dose. (This holds true even if the dosing interval is not fixed)

Front 4

List 5 situations in which superposition would not be valid.

Back 4

1. Drug does not follow linear kinetics

2. A drug's carrier system gets saturated (for instance, drug is eliminated by a saturable enzymatic process and so follows michaelis-menton kinetics; recall Vmax and Km)

3. There is enzyme induction

4. There is enzyme inhibition

5. The patients disease condition changes significantly between doses

Front 5

What is the point of multiple dosing?

Back 5

It is intended to keep plasma drug levels within the therapeutic window.

Front 6

In multiple dosing what may be adjusted to to keep plasma drug levels within the therapeutic window?

Back 6

The dose and time between doses.

Front 7

In multiple dosing when will accumulation fail to occur?

Back 7

Accumulation will not occur if a second dose is given at a longer interval than that required for the elimination of the previous dose.

Front 8

During accumulation what should eventually be achieved?

Back 8

Steady state should eventually be achieved. This means Cmax and Cmin should remain the same from dose to dose.

Front 9

If there is no accumulation, steady state Cmax for a later dose is the same as what?

Back 9

Cmax for the first dose.

Front 10

For drug safety Cmax should always be what?

Back 10

Should always be less than the minimum toxic dose.

Front 11

What does accumulation depend on?

Back 11

Accumulation does not depend on the dose. It depends on the dosing interval and the elimination rate constant.

Front 12

The time reqd to attain steady state is dependent on the ? but is independent of ? or ?.

Back 12

The time reqd to attain steady state is dependent on the elimination half-life but is independent of dose or interval between doses.

Front 13

In drug accumulation for iv infusion administration ka is ?.

Back 13

ka is rapid >>> k

Front 14

The time need to reach:

1. 90% steady state conc?

2. 99% steady state conc?

Back 14

1. 3.3 t1/2

2. 6.6 t1/2

Front 15

In drug accumulation the number of doses needed to reach steady-state is dependent on what?

Back 15

t1/2 and time interval between doses.

Front 16

When speaking of drug accumulation what does f represent?

Back 16

f is the fraction of the dose remaining in the body.

Front 17

What does f depend upon?

Back 17

k and time interval between doses.

Front 18

If the time interval between doses is small then f is ?.

Back 18

Then f is large.

Front 19

F = fraction of dose absorbed. For an IV dose what does F equal.

Back 19

F = 1

Front 20

In drug accumulation the difference between the max and min amts of drug in the body is equal to what?

Back 20

The difference between the max and min amts of drug in the body is equal to the administered dose. (original dose)

Front 21

In a plasma level eqn at ss e^-nkT is equal to what?

Back 21

It approaches zero.

Front 22

The more ? a missed dose is, the greater effect it will have on the ?.

Back 22

The more recent a missed dose is, the greater effect it will have on the current plasma concentration.

Front 23

Missed doses greater than ? ? ? later should be omitted because of their minimal impact.

Back 23

Missed doses greater than 5 half-lives later should be omitted because of their minimal impact.

Front 24

For repeat IV infusions, intermittent short IV infusions prevent what? What does this mean?

Back 24

Intermittent short IV infusions prevent transient extreme high plasma levels of a drug and so are better tolerated even though steady-state may not be attained.

Front 25

In repeat IV infusions what does D represent? R? tinf?

Back 25

D is the size of the infusion. R is the infusion rate. tinf is the duration of the infusion.

Front 26

What is the point of a loading dose?

Back 26

It is used to achieve the desired plasma concentration (Cav) promptly, circumventing the delay that the process of absorption introduces.

Front 27

When determining a loading dose; when the dosage interval is equal to the half-life, the dose ratio has a value of what?

Back 27

2

Front 28

In multi-dose regimens an estimation of what is difficult? Why?

Back 28

An estimation of ka is difficult with multi-dose regimens because of superposition of doses.

Front 29

The determination of bioavailability is possible when?

Back 29

At steady state.

Front 30

When should the first sample be taken?

Back 30

Just before admin. of the 2nd dose, thereafter, doses should be taken regularly after the administration of each dose.

Front 31

Multi-dose regimen bioavailability studies can reveal what?

Back 31

They can reveal changes that would not be obvious in a single dose study. For example, the existence of non-linear kinetics, drug-induced malabsorption syndrome, etc,.

Front 32

What can be designed to ascertain bioequivalence? Explain.

Back 32

A multiple dose study. Equal doses of test and a reference product may each be administered repeatedly in turn (two-way cross-over) to steady state, separated by a time period required to completely eliminate the drug from the body. The AUC and Cmax of the test product should be w/n 80-125% of the corresponding values for the reference product using a 90% confidence interval.

Front 33

The area under a plasma drug concentration vs time curve is a measure of what?

Back 33

It is a measure of the amount of drug exposure.

Front 34

What can a high fecal drug conc. indicate?

Back 34

It can be an indication of biliary secretion after systemic absorption.

Front 35

Urine concentration of a drug is NOT what?

Back 35

It is not a DIRECT indication of the systemic conc. of the drug.

Front 36

Saliva drug conc.s assayed after equilibrium with plasma drug conc.s is an ? measure of ?.

Back 36

Saliva drug conc.s assayed after equilibrium with plasma drug conc.s is an indirect measure or drug levels in the body.

Front 37

What may be used to explain drug interactions.

Back 37

A pharmacokinetic model.

Front 38

In a 2-compt. model, at steady state, what is equal?

Back 38

In a 2-compt. model, at steady state, the central compt. is equal to the conc. of the drug in the peripheral compt.

Front 39

In a 2-compt model at steady state what is equilibrated?

Back 39

The drug between the central and peripheral compt.s

Front 40

In the 2-compt model the rate of drug diffusion into the central compt. is equal to what?

Back 40

It is equal to the rate of drug diffusion from the central compt.

Front 41

In a 2-compt model, upon equilibration, the rate of drug entry into the peripheral compt equals what?

Back 41

The rate of drug entry into the peripheral compt equals the rate of exit.

Front 42

In a 2-compt model the volume of the central compt is greater than what?

Back 42

In a 2-compt model the volume of the central compt is greater than the volume of distribution determined by area.

Front 43

In a 2-compt model the vol. of distribution determined by area is dependent on the value of the what?

Back 43

It is dependent upon the value of the rate constant of the beta phase.