CB - Mathematical Principles in Pharmacokinetics Flashcards
How can we analyse the concentration-time curve in order to understand what happens to the drug in the human body?
AUC - The total amount of drug that has entered the general circulation
SLOPE - Allows rates of change to be calculated
How is bioavailability (F) calculated? And how does dosage affect this?
The fraction of an oral dose which reaches the systemic circulation as the parent compound
- Is calculated as the ratio of the AUCoral to the AUCiv
If the dosage is the same you can calculate F by dividing AUCoral by AUCiv
If the dosage is different you have to multiply this division by the DOSEiv/DOSEoral
What does the one-compartment and two-compartment model in distribution assume?
One-compartment model
- Assumes instantaneous distribution (monophasic)
Two-compartement model
- Assumes time to distribute to tissues
What is Ɑ and Cp when referring to a log[Plasma]-time graph?
Ɑ - Is the initial rate of decrease in plasma concentrations after an i.v bolus dose
(rate of distribution - gradient of Cp)
Cp is the change in the [DRUG] in the plasma
What is Vd and how do you calculate it for a one-compartment model and two-compartment model?
For a one-compartment model:
Assumes the drug distributes instantaneously to all tissues
- At time 0 the full distribution has already taken place
- Extrapolate back to the y-axis and use this as C0 value
For a two-compartment model:
At t=0, very little distribution will have occurred
- Take elimination phase and extrapolate back to y-intercept (uses theoretical concentration if all the drug was fidtributed instantaenously)
What are some features of Vd? (6)
- Dependent upon the physiochemical properties of the drug
- An indication of the extent of tissue uptake of the drug
- Independent of dose
- The volume of plasma in which the dose APPEARS to have dissolved
- A non-physiological ‘dilution factor’
- Presented as L/Kg
Describe first-order kinetics in elimination
Rate of elimination is proportional to the drug concentration.
Rate of Elimination (k) is directly proportional to clearance (CL) and inversely proportional to the apparent Vd
k = CL/Vd
What is CL and how can it be calculated?
CL
The volume of plasma cleared of drug per minute
- Depends how good the body is at eliminating the drug
- Is a specific value for each drug
- CL value will be very similar related to the blood flow of the organ it is being eliminated from
CL = (DOSE x F) / AUC
What is the general formula for half life and what are its properties?
Half life (t1/2) = 0.693 / k
Shorter half life = Rapid elimination
- Half life is independent of concentration
- Half life is a specific value for each drug
- Half life is altered by inducers and inhibitors
Define steady state (Css) and how it is achieved
Css is when the rate of drug intake equals the rate of drug elimination.
- Achieved after 5 times the elimination half-life
Css = rate of infusion / clearance
What is Multiple Dosing and how can it influence Css?
MULTIPLE DOSING
Maintain a constant concentration in the blood, by repeated oral dosing
The Css for a drug can be changed by:
1. Changing the DOSE of a drug
2. Changing the DOSE INTERVAL
Css =
(DOSE x F) / (DOSE INTERVAL x CL)
A shorter interval produces a higher Css
How is the delay in reaching Css avoided with long half-life drugs?
By giving a large first dose (loading dose)
- Loading dose (I.V) = Css x Vd
- Loading dose (oral) = Css x Vd / F
Remember equations in red box on slides
