2 Pharmacokinetics Applications Flashcards
Describe bioavailability (f) - and how can it be shown
Bioavailability (f):
- implicates fraction of an orally administered dose that reaches systemic circulation as an intact drug
i.e. the fraction (of drug) absorbed
It can be shown as an AUC(oral)/AUC(IV) graph
State what can influence an overall plasma level (of drug)/time curve [for single oral dosing]
- Rate of dissolution (of tablet)
- Rate of absorption
Describe the course of a rapid release formulation drug on a concentration/time graph
The rise to the peak is very quick - this is the stage where absorption and elimination are occurring
- Gives rapid response
- (e.g. dosage is 3 tablets a day)
- BUT, has a lot of side effects (on the peak)
Describe the course of a modified release formulation drug on a concentration/time graph
Has fast rise to the peak (not as fast as rapid release), but will have lower side effects than rapid relief
- (e.g. dosage is 1 tablet a day)
Describe the course of a sustained-release formulation drug on a concentration/time graph
- Prolonged absorption superimposed on the elimination
- half-life is not a true elimination half
> ‘context-sensitive half-life’ - These drugs have a slower rise to the peak
- They give a lot longer range in the therapeutic window
- Hence, it can increase patient compliance)
- (e.g. dosage is 1 every 2 days)
- Less likelihood of/no side effects
What is the steady-state concentration (Css)?
Steady-state concentration is the concentration of drug at which:
- the rate of absorption of drug = rate of elimination of drug
How many half-lives does it take to achieve a steady state?
It takes approx. 5 half-lives
- After 5 doses, the majority of the drug (96.9%) is in the systemic circulation, meaning a steady state is near enough reached
What is the t1/2?
Half-life -
- the time for the drug plasma concentration to decrease by 50%
Give the problem associated with giving more than one dose, when trying to achieve a steady-state concentration
- If the doses are given sufficiently far apart in time, each dose will behave independently
- And thus not produce a steady-state
Give the formula which can be used to calculate the oral regimen (of drug administration)
CL x Css x tau
Dose = ___________________
F
- CL: clearance
- Css: steady-state concentration
- Tau: dosage interval (can be hours or days)
What is the calculation needed to counteract the ‘first-pass metabolism’ effect when administering a drug?
(as the drug can be lost from total dose)
- To compensate for the amount of drug that is lost (1st pass metabolism), you then divide by f (bioavailability)
- to get the extra amount to give to compensate for this
State 3 factors that can affect the design of a dosage regime:
- Therapeutic Window (TW)
- Urgency of Onset of Effect
- Elimination half-life
Describe how Therapeutic Window can affect the design of a dosage regime:
Large TW means there is a ‘maximal dose’ strategy
Small TW means there is a ‘target level’ strategy
- small TW can be problematic, as it can be very easy for the concentration of the drug to dip below the therapeutic levels, or for it to go into toxic levels
Describe how Urgency of Onset of Effect can affect the design of a dosage regime:
May have to give a loading dose (LD)
- to achieve the TW rapidly - rapid rise to Css
- LD = target level x (Vd/F)
Followed by a maintenance dose (MD)
- to keep up with rates of elimination (and keep drug concentration in the TW)
- MD = target level x (CL/F)
Describe how Elimination half-lives can affect the design of a dosage regime:
Short t1/2:
- Large TW: large dose at convenient intervals (6-8 hours)
- Small TW: given by infusion +/- loading dose
Moderate t1/2:
- Give initial dose, then half that every half-life
Long half-life:
- Set a 24-hour dose interval to ensure best patient compliance
