Drug Dosing Regimens

Question 1

What is the therapeutic range?

Answer 1

1. Range of drug concentration having a high probability of causing desired effect and low probability of causing toxic effect
2. Only relevant for approx. ~80% of cases
3. Therapeutic range lies between the minimum effective concentration and minimum toxic concentration

Question 2

What is the steady state concentration?

Answer 2

1. Time in which the concentration of drug in body stays consistent
   a) This helps to maintain the desired pharmacological response whilst avoiding toxicity
2. Achieved by:
   a) Continuous administration
   b) Multiple dosing via other routes

Question 3

Describe the plasma concentration-time profile for a drug administered orally or parenterally:

Answer 3

1. Diagram
2. Diagram
   a) Bolus means all at once so it starts high and slowly tails off

Question 4

What is the drug clearance?

Answer 4

1. The volume of blood cleared irreversibly of drug per unit of time
   a) Measured in L/hr or mL/min
   b) Ability of an organ or the body to eliminate the drug
2. Total systemic clearance CLs = CLhepatic + CLrenal + CLother
   a) Elimination rate (mg/h) = CL (L/hr) x [plasma concentration of drug]
3. For a particular drug in a healthy individual, clearance is constant

Question 5

What is hepatic clearance?

Answer 5

1. Clearance of drugs in liver is due to drug-metabolising enzymes
2. Hepatic extraction ratio = CLhepatic / hepatic blood flow
   a) If drug does not metabolise, then hepatic clearance = 0
   b) If all of the drug metabolises, then hepatic clearance = hepatic blood flow (hepatic extraction ratio = 1)
   c) If hepatic clearance is 30 L/hr, and hepatic blood flow is 90 L/hr then for every blood cycle through liver only 1/3 of the drug is metabolised by the liver (the other 60 could be metabolised by other parts of the body)

Question 6

What is renal clearance?

Answer 6

1. Occurs due to basic renal processes of glomerular filtration, tubular reabsorption, and tubular secretion
2. Kidneys are responsible for clearing water soluble drugs
3. Liver converts fat soluble drugs to water soluble drugs and then the kidneys clear it

Question 7

What is the volume of distribution?

Answer 7

1. The volume in which amount of drug in body would need to be uniformly distributed to produce observed concentration in blood
   a) = to total amount of drug in body / plasma drug concentration
2. Theoretical concept
   a) Certain drugs may not stay in blood stream and may bind to tissues meaning their volume of distribution will be larger
   b) Certain drugs however stay in intravascular distribution and so distribution will be similar to plasma volume

Question 8

What is drug half-life time?

Answer 8

1. Time taken for the plasma concentration of drug to decrease by half
2. Major determinant of:
   a) Duration of drug action after single dose
   b) Time taken to reach steady state concentration
   c) Dosing frequency
3. Diagram 2

Question 9

What is first order kinetics?

Answer 9

1. Constant proportion of drug is eliminated per unit of time
2. If dose and plasma concentration of drug increases, rate of elimination increases

Question 10

What is zero order kinetics?

Answer 10

1. Saturable metabolism
2. Enzymes reach capacity so rate of metabolism cannot increase further as dose increases
3. Rate of elimination does not increase in proportion to dose and concentration