6. Pharmacokinetic modelling. Principles of pharmacotherapy Flashcards
Pharmacokinetics describes changes in…
Plasma drug conc. over time
Pharmacokinetic models
Relatively simple mathematic schemes that represent complex physiological spaces or processes
- Amount of drug in tissues is generally related to plasma conc.
Zero-order elimination
Occur when therapeutic doses of drug exceed the capacity of elimination mechanisms
- Plot concaves upwards
- Constant amount of drug will be eliminated per unit time
First-order elimination
Occurs when elimination systems are not saturated by drug (most drugs)
- Linear function of plasma drug conc.
- Elimination of a constant fraction of drug per unit time
One compartment open model
Body seen as one continuous fluid phase into which drug is administrated & diffuses
Open (continuous loss of drugs from compartment due to metabolism & excretion)
Half-life
Time taken for plasma drug conc. to be reduced by 50%
- Only applies to drugs eliminated by first-order kinetics
- Log plasma drug conc. vs. time profile for drugs fitting in one compartment
- Related to:
- Elimination rate constant (k)
- Volume of distribution (VD)
- Clearance (CL)
- Drug eliminated in time interval equal to 5 half lives
Two compartment open model
How the body mostly behaves
- Rapid change in plasma conc.
- Linear ↓ in log drug conc.
- Central compartment → equilibrium
- Peripheral compartment → equilibrium
- Distribution
- Elimination
Two compartment open model: Rapid change in plasma conc.
Distribution phase
- Time required for drug to reach equilibrium distribution between central & peripheral compartment
Two compartment open model: Linear ↓ in log drug conc.
Observed if elimination phase is first order
Two compartment open model: Central compartment → equilibrium
- Blood
- Intestinal fluid
- Highly perfused organs (heart, liver, lung, kidney)
Two compartment open model: Peripheral compartment → equilibrium
Less perfused organs
- Skin
- Bone
- Fat
Two-compartment open model: Distribution
Exponential
Two compartment open model: Elimination
Linear
Non-compartment PK analysis
Artificial mathematics has no direct relationship to physiological space
- Dependent on estimation of total drug exposure, most often estimated by area under the curve methods
Give the principles of pharmacotherapy
- Repeat administration
- Steady state
- Loading dose
- Maintenance dose
Repeat administration
If the drug eliminated by first-order kinetics is administered repeatedly, average plasma conc. of drug will ↑ until mean steady state is reached
Time interval required to reach steady state =
5 half-lives
Steady state
Average between high point after administration and low point just before next administration
- To maintain dose range, must be equal to elimination rate
Loading dose
= desired drugplasma x VD
- After loading dose we give maintenance dose → Steady state
Maintenance dose
= desired drugplasma x CL
- Dose required per unit time to maintain desired steady-state level in plasma
