Intro to PK

Question 1

What makes something a poison?

Answer 1

The dose

Question 2

What is drug therapy?

Answer 2

Planned action that involves risk of unwanted adverse effects

Question 3

How is a drug dose chosen?

Answer 3

Based on its ability to achieve and maintain therapeutic (target) concentrations producing minimal adverse effects in the body

Question 4

Define appropriate dosage regimen

Answer 4

1. Therapeutic window between MTC and MEC
2. To achieve and maintain safe and effective therapy

Question 5

What are components of appropriate dosage regimen?

Answer 5

A: Right drug
B: Dose of a drug
C: Dosage form
D: Route of admin
E: Dosing interval/frequency
F: Duration of therapy

Question 6

What information do we need to design appropriate dosage regimen?

Answer 6

1. Therapeutic range of the drug
2. PK parameters of the drug

Question 7

What is a therapeutic range of a drug?

Answer 7

1. Minimum (Cmin) and maximum (Cmax) plasma drug concentration values

Question 8

Where are therapeutic range values found?

Answer 8

1. Between MEC and MTC
2. Estimated average plasma concentration (Cavg)/Css

Question 9

What are the PK parameter of a drug?

Answer 9

Vd, CL, Half-life

Question 10

How does Vd effect loading dose?

Answer 10

It relates plasma concentration to the amount of drug in the body

Question 11

What is LD?

Answer 11

A large initial dose given to achieve therapeutic drug levels from the beginning

Question 12

How is Cl used to determine maintenance dose (dosing rate)?

Answer 12

It measures the rate of drug elimination that needs to be replaced to maintain therapeutic concentration

Question 13

What is another name for Cmax

Answer 13

MTC

Question 14

What is another name for Cmin?

Answer 14

MEC

Question 15

What is MD?

Answer 15

Given at fixed intervals to keep drug concentrations within the therapeutic concentration range

Question 16

Why is half-life used for dosage regimen design?

Answer 16

It affects the time to reach Css and determines the shape of the plasma concentration-time courses

Question 17

What are all the PK parameters used to estimate plasma concentration-time profiles?

Answer 17

1. Vd
2. Cl
3. T1/2
4. Cmax
5. Cmin
6. Cavg/Css (therapeutic range)
7. Tmax
8. AUC
9. F

Question 18

What are parameters?

Answer 18

Observable quantities that remain constant for every state of a system

Question 19

What is the purpose for PK?

Answer 19

To study ADME processes of drugs in the body to examine the time course of drug concentrations in mainly plasma, and also in urine and bile

Question 20

What are the methods used to analyze plasma drug concentration-time profiles?

Answer 20

1. Non-compartmental analysis techniques (NCA)
2. Compartmental model fitting methods

Question 21

What is another name for NCA?

Answer 21

Model-independent approaches

Question 22

What is are the approaches of NCAs?

Answer 22

1. Applies the trapezoidal rule for measuring AUC
2. Estimates Cmax using tmax directly from the data and Cl, k, t1/2, and Vd driven equations

Question 23

How does the compartmental model fitting methods help determine PK parameters?

Answer 23

1. Provide a continuous description of drug concentration
2. Consider the body as a finite number of interconnected, well-mixed, homogenous compartments
3. Mathematical PK models are developed using nonlinear regression methods to estimate PK parameters
4. drug concentrations over a time range are predicted using the developed PK model to estimate Cmax , tmax , Cavg / Css , AUC, F

Question 24

What are the PK approaches of designing dosage regimens?

Answer 24

1. Individualized dosage regimen (Patient-specific values)
2. Dosage regimen based on population values
3. Dosage regimen based on partial PK parameters (Bayesian approach)

Question 25

What is individualized dosage regimen?

Answer 25

The dose is calculated based on the PK parameters of the drug derived from individual patient drug concentrations measurement in plasma

Question 26

How is a dosage regimen designed based on population values?

Answer 26

Regimen is calculated based on population average PK parameters obtained either from package insert or from clinical studies published in the drug literature

Question 27

How is a dosage regimen designed based on partial PK parameters (Bayesian approach)?

Answer 27

The use of population PK uses average patient population characteristics and only a few plasma concentration from the patient

Question 28

What is PK used for?

Answer 28

1. Calculate LD and MD 2. Determine drug dosage regimen 3. Perform dosage adjustments in patients with renal and hepatic diseases 4. Perform BA/BE studies 5. Predict drug-drug and drug-food interactions