Pharmacokinetics 5-6 Flashcards
Why are pharmacokinetics important?
- determine drug behavior
- safe & effective dose in animal systems
- optimization of therapeutic conc.
Bioequivalence
Comparing new drug w/ known version
Dosage regimen
Absorption + distribution + elimination
AUC (area under curve)
- total amt. of drug that comes into systemic circulation
- helps evaluate bioavailability of drugs
- represents extent of absorption
- expressed as product of drug conc. and time
Trapezoidal rule
- divide plasma conc.-time profile into several trapezoids
- add the AUCs of all the trapezoids
Volume of distribution (Vd)
- Vd= Dose/Plasma conc
- higher tissue dist.->more lipid soluble; mainly tissues
- lower tissue dist. -> more H2O soluble; plasma mainly, maybe tissue
- dose must be given IV
Protein bound Vd
- plasma only
- 5% body wt.
H2O soluble Vd
- extracellular fluid
- 20-30% body wt.
Lipid soluble Vd
- plasma (mostly), ECF and ICF, or Total body water
- 60-70% body wt.
Elimination kinetics
- k= elimination rate constant
- 1st order kinetics more common than zero order
- determines dosage; dose interval; duration in body
First order kinetics
- most common
- Fixed fraction of drug processed
- constant 1/2 life
- usually eliminated in 5 half lives
Zero order kinetics
- fixed amt. of drug processed per time
- not usually common
- 1/2 life dependent on dose given
Clearance rate
Cl= (dose/AUC) * (vol/time)
Half life
- t 1/2= 0.693* Vd/Cl
- shorter= rapid elimination
- good way to determine dosing intervals
- entero-hepatic circulation and plasma protein binding increase 1/2 life
- may increase in renal or hepatic dysfunct.
Dose
Amt of drug administered to produce response
- Dose= Cmax * Vd
Dosing interval is determined by
Max. plasma conc. dropping to point below which desired response no longer occurs
Steady state concentration
- Css (symbol)
- most drugs reach state in 3-5 half lives
- when conc. remains stable/consistent when drug is given repeatedly or constantly
What single variable allows you to determine how long it will take to reach a steady-state drug level?
Elimination half life
3 compartment PK models
- 1 compartment
- 2 compartments
- non-compartmental
One compartment PK model
- rapidly distr. drugs
- whole body a single, kinetically homogenous unit
Two compartment model
- central compartment: highly perfused organs
- peripheral compart.: less perfused organs
Non-compartmental
- no compartments
- PK parameters obtained by algebraic equations
