Clinical Pharmacokinetics Flashcards
What is a dosage regimen ?
This is a plan for a drug administration over a period of time
It should result in therapeutic levels of the drug in blood without exceeding the minimum toxic concentration
What is maintenance dose?
To maintain the plasma concentration within a specified range over long periods of therapy, a schedule of maintenance doses is used
What is the loading dose?
If it’s necessary to achieve a target plasma level rapidly, a loading dose is used to load the Vd with the drug
What is the dosing plan based on?
The. Knowledge of:
-therapeutic window
- clearance
- Vd
What is the therapeutic window?
- Determines the range of plasma levels acceptable when designing dosing regimen
- The minimum effective concentration determines the trough plasma concentration
- the minimum toxic concentration determines the peak plasma concentration
Explain in detail maintenance dose
In most clinical situations drugs are administered to maintain a steady state of drug in the body:
- Just enough drug is given in each dose to replace the drug eliminated since the preceding dose
- A drug will accumulate until the amount administered per unit time is equal to the amount eliminated per unit time
- The plasma concentration at this point is called the steady-state concentration (Css)
Thus if the desired target concentration is known, the clearance in that patient will determine the dosing rate
If intermittent doses are given, the maintenance dose is calculated with:
Maintenance dose= dosing rate x dosing interval
At steady state, what is the dosing rate and rate of elimination
D9ding rate (rate in)equals elimination rate(rate out)
What is the formula of dosing rate?
Dosing ratess = rate of eliminationss= (CL x C)/F
Explain Continuous IV injection
With continuous IV infusion, the rate of drug entry in the body is constant
The plasma concentration of drug rises until the rate of drug eliminated from the body balances input rate
A steady-state is achieved in which drug concentration remains constant
Rate of elimination = CL x C
Css is achieved when drug rate of elimination = rate of administration
Css= infusion rate/ CL
- CL is constant for drugs showing first order kinetics
- Therefore the steady- state plasma concentration (Css), is directly proportional to the infusion rate
- If infusion rate is doubled, steady-state plasma concentration is doubled
How is the approach to steady state handled for IV infusion?
The rate of approach to steady state follows first order kinetics
50% of the final steady-state(Css) is attained after 1 half-life
- 75% after 2 half-lives
- 87.5% after 3 half lives
- 93.75% after 4 half lives
It can be assumed that steady state is reached after about 4 half-lives
When infusion is stopped, plasma concentration declines to zero with same time course observed in approaching steady state
How is the loading dose calculated?
If the therapeutic concentration must be achieved rapidly and the Vd is large , a large loading dose may be needed at the onset of therapy:
This is calculated as follows:
Loading dose: (Vd x TC)/ F
Fixed doses result in…
Fluctuations in the plasma level of the drug
What happens of we give a single IV injection?
The plasma level will peak and decrease exponentially with time
What happens if we give multiple IV injections?
When the drug is given repeatedly at regular intervals, plasma concentration increases until a steady state is reached.
The plasma concentration fluctuates about a mean
What happens if we give multiple smaller doses of an IV injection?
Giving smaller doses at shorter intervals reduces the amplitude of the swings in drug concentration
-The drug Css and the rate at which steady state is approached aren’t affected by dosing frequency
