GP 17 - Clinical Pharmacokinetics 2

Question 1

What are the following:

• Dosage regimen
• Maintenance dose
• Loading dose

Answer 1

• Dosage Regimen - a plan for drug administration over a period time so that therapeutic levels of the drug are maintained in the blood without exceeding the minimum toxic concentration
• Maintenance doses are doses of a drug given at particular times to maintain the plasma [drug] within a specified range over long periods of therapy
• A loading does is a drug dose used to achieve a target plasma [drug] rapidly

Question 2

What is Dosing rate_ss and how is it calculated?

Answer 2

Dosing rate_ss is the amount of drug given to just replace what the body has eliminated since the last dose was given. Therefore,

Dosing rate_ss = rate of elimination_ss = CL*C/F

Question 3

What is dosing interval?

Answer 3

The time between doses are given

Question 4

How is the maintenance dose calculated?

Answer 4

Dosing Rate*Dosing Interval

Question 5

How is C_ss calculated?

Answer 5

Infustion rate/CL

Question 6

How is the loading dose and dosing rate calculated for a given TC (target concentration)?

Answer 6

Loading Dose = (V_d*TC)/F

Dosing Rate = (CL*TC)/F

Question 7

What is PC1 and PC_ss?

Answer 7

When a drug is given repeatedly at regular intervals, the peak plasma concentration after each dose increases until it reaches a steady state. That steady state concentration is the PC_ss

The peak concentration after the very first dose is given is the PC1

Question 8

What is an accumulation factor (AF)? How is it calculated? What is it used for?

Answer 8

AF = 1/fraction of drug lost during the dosing interval

The AF predicts the ratio of the PC_ss to the PC1. Therefore it is used to predict what the PC_ss will be once the PC1 is known.

PC_ss = PC1*AF

It can also be used to determine what the loading dose should be:

Loading Dose = Maintenance Dose*AF

Question 9

What is the AF of a drug given once every half-life?

Answer 9

2

Question 10

How does dosing frequency affect the C_ss?

Answer 10

It doesn’t, it only affects the PC swings

Question 11

How will an IV administration [drug] vs time graph be different from an oral administration [drug] vs time graph?

Answer 11

The IV grapth will have a very sharp (almost vertical) increase to the PC and immediately start declining exponentially.

The oral administration graph will have a more gradual increase with a rounded peak, followed by an exponential decline.

Question 12

Why would a “slow release” oral administration want to be used instead of a “rapid release” one?

Answer 12

If the [drug] does not have to be very high, slow release formulations will have more delayed and stretched out concentration peaks which allow for less frequent administrations of drugs with short half-lives

Question 13

The desired IV dosing rate for a drug is 28mg/h. The decision has been made to switch the patient to an oral tablet of the medication. If the tablet is to be taken twice a day and its F = 0.96, what mg tablet should the doctor prescribe?

Answer 13

Dose_oral = (Dosing Rate_IV/F)* dosing interval

350mg

Make sure rate and interval are the same units

Question 14

What is the relationship between [drug] and drug effect?

Answer 14

E = (E_max*C)/(C+EC₅₀)

Question 15

Describe the three regions of a time course drug effect graph.

Answer 15

• [drug] > EC₈₀ - the drug response is fairly high and decreases very little (it’s almost a horizontal line) despite large changes to [drug] in this range
• EC₈₀ > [drug] > EC₂₀ - the drug response decreases in a gradual linear fashion
• [drug] < EC₂₀ - the drug response decreases exponentially in a manner almost parallel to the [drug] decrease

Question 16

How does doubling a drug dose affect the drug response?

Answer 16

Doubling a drugs dose, extends its effectiveness by one half-life