pharmacokinetics 2 Flashcards
bioavailability
1) bioavailability
how much reaches systemic circulation
- relative measure of drug absorption
2) absolute bioavailability (F) = AUCrouteX/AUCiv
3) relative bioavailability (F)
- more likely to compare two different preparations than IV comparison
bioequivalence
1) if drug acts through absorption through bloodstream
2) bioequivalent products show no difference in rate and extent of absorption of a therapeutic ingredient
3) functional related drugs have comparative bioavailability
4) therapeutic equivalence
- therapeutically equivalent can be substituted and produce same clinical effect
- much be bioequivalent, same active ingredient, route of admin, and strength
one compartment model
1) one compartment model
- body is a single well mixed container = volume of distribution for that drug
- drug distributes immediately after admin
- drug is freely removed by metabolism or excretion
- elimination from plasma is a straight line (log scale) with exponential decay
multicompartment model
1) when drug accumulates in different compartments prior to distribution
2) for many, two compartments are sufficient
- heart, lung, and brain (1), and rest of body (2)
- biphasic curve
- linear plasma elimination phase, with initial exponential distribution phase
zero order vs first order kinetics
1) describe rate of elimination
2) most drugs follow first order, few follow zero model (alcohol, phenytoin)
zero order
1) rate of elimination is independent of the drug concentration
2) elimination route is saturated
3) constant % of drug lost per unit time
- elimination rate constant
first order
1) dose dependent elimination from plasma
2) constant amount of drug list per unit time
first order kinetics equation
1) C(t) = C0e^-kt
2) plasma drug concentration at time t
- exponential elimination rate can be seen if plotted
fist order kinetics and half life (t1/2)
1) plotting plasma drug concentration against time
- drug disappearance curve
2) plasma half life
- time taken for plasma drug concentrations to fall to half of original levels
- calculated from time of administration and is constant for any drug
3) pharmacologic half life
- pharmacologic effect decays by half
- irreversible receptor binding means PharmHL > PlasmaHL
4 )but for most, both are about the same
dose does not affect t1/2
1) starting concentration does not influence half life
2) if C0 is high, elimination rate is high, and vice versa
elimination rate constant
1) drug concentration remaining in the plasma can be calculated
2) C(t) = C0e^-kt
- we know C1, and t
3) the rate constant is k = 0.69/t1/2
- we usually know t1/2
4) so we can calculate drug concentration at any given time
example calculation
1) t1/2 = 1 hr
2) dose 100 mg
3) patient aches at 12.5 mg is remained in the blood
4 )what is the time?
C(t) = 12.5 mg, C0 = 100 mg, t1/2 = 1 hr
what is k?
k = 0.69/1 = 0.69
solve equation for t
t= 3 hours
zero order kinetics equation
1) C(t) = C0 - k01
- elimination pathways are easily saturated at low levels of drug, so rate of elimination is a CONSTANT
2) constant amount is lost per hour
- ex. alcohol
multiple dosing
1) if a second dose is admin befroe the original one is eliminated, the doses are cumulative
2) the time period between doses is td (dosing interval)
3) if td is maintained the same, the peak dose will reach a point where it does not increase any further
- plateau/maintenance state
- with first order kinetics, the rate of elim will increase if more is admin
4) drug swing = concentration between peak and trough
maintenance state equations
1) dose = Cmax(1-e^-ktd) where k = 0.69/t1/2
2) maintenance dose from this equation can be calculated with known dosing interval and Cmax
