Final Pharmacokinetics Flashcards
Dose Rate =
<p>(CL)*(SS Conc)</p>
Equation for renal clearance
CL = Filtration + Secretion - Reabsorption
Markers for GFR
Creatinine and Inulin
Renal Dosage Adjustment Equation
= Average Dose * (Creatinine Clearance/100(normal))
When should you worry about adjusting for renal clearance
When kidneys do at leas half the clearing and fxn is at least half down
Characteristics of first order elimination
Elimination of a drug that is within its therapeutic range of concentration. In this condition, elimination is proportional to a percentage. Cp is linearly accumulated with dose.
Maintenence Dose Equation
DR = CL * Css
What makes zero-order elimination different than first order?
At their therapeutic concentration, the drug elimination capacity is saturated. This is caused by complete usage of the enzymes/transporters
Relationship of drug elimination and drug concentration in zero order rxn? first order rxn?
0 – Linear
1 – Exponential
The accumulation of drug concentration in zero-order rxns is….
Non-linear
Three go-to zero order drugs
- Ethanol
- Phenytoin
- Aspirin
In first order elimination, drug elimination occurs at a ______ rate
Exponential (Same percentage cut every time)
In zero order elimination, elimination occurs at a _____ rate
Linear (Same AMOUNT of drug lost each time)
In first order dosing, Plasma concentration is ____ accumulated with dose
Linearly
In zero order dosing, plasma concentration is
non-linear
Michaelis-Menton Equation
Elimination Rate = (Max Velocity of rxn)(conc) / (Drug conc at 50% Vmax) + C
What does Vmax refer to?
The max velocity of a reaction at a very high drug concentration
What does Km refer to?
The drug concentration at 50% of Vmax
A measure of affinity of the substrate for the enzyme
According to Michaelis-Menten, If a system is not saturated, increasing concentration will _____ elimination. When the rate is at its max, elimination will _____ with increases in concentration.
Increase
do nothing. no increase in conc.
When asked for assumptions for the models in the last PK lecture, always write
Elimination must be first order
What is half life
The time is takes to eliminate 50% of a drug from the body
What is the Elimination Rate constant?
Fraction of the drug eliminated/time
Equation for elimination rate constant
Clearance/Vd
What is elimination rate
The amount of drug elimintated/time
Equation for half life
=0.693 * (Vd/CL)
or
0.693 / Ke
One more time – the constant number you’ll probably forget on the test that’s in that stupid halflife equation.
0.693
In first order rxns, what do increases in drug concentration do to half life.
Nothing.
How does a decrease in CL influence halflife?
Makes it longer
How does a bigger Vd influence halflife?
Makes it longer
Why use a semi-log plot?
makes conc/time linear to provide a slope that correlates with Ke?
True or False. Clearance concepts are not applicable once the concentration pushed into saturation.
True
______% of the final plateau reached after 4.5 half lives
____% of the total dose eliminated after 4.5 half lives
95
Three reasons to give a shit about half life
Used to determine time to steady state w/ chronic dosing
Used to determine duration of action
Used to determine dosing frequency
95% of the Css will be reached after _____ half lives.
4.5
Doubling a dose will increase the duration of action by….
One half life
Why does it matter if you check half life when managing dosing frequency
Its required to avoid too large fluctuations in plasma conc during the dosing interval
Benefit of increased frequency of doses
Less fluctuations in Cp
The extreme – IV injection – No fluctuation
AUC of 1st dose =
AUC of 1 interval at Css
The semilog CT curve can be described with what equation
Cpt = Co * (e)^-kt
What does it mean if a drug cannot be described by the straight line on the semi-log CT curve?
It must be a multi compartmental model
What # compartment model
2-compartment model is the most common
First order Vd=
Dose/Cp
Why might it be important to know the -Ke in a Vd with elimination graph?
Elimination Rate Constant (the slope) can be used to extrapolate a value for Co when a measured concentration can’t be found.
When in the one-compartment model on the linear graph,
Cp at a given time is equal to…
Coe^(-Ket)
Assumptions used for the one compartment model
Must be first order
Body one homogenous compartment
Instantaneous mixing
Distribution between compartments is _____ than distribution within a compartment
slower
Distribution phase is typically about how long?
1-2 hours
Once a concentration has distributed…the concentration is _____
even
Material in this course assumes that compartment and concentrations are in …..
post distribution phase
Equation used for two compartment model (see page 17 of the notes if the typed version looks like a fucking mess)
Cp = Ae^(ket) + Be(ket)
Maintenance dose rate for IV:
DR = CL*Css
Maintenance dose rate for PO:
=CL*(Css/F)
Loading dose for IV:
=Vd*target Cp
Loading dose for PO:
=(Vd*target Cp) / F
Dosing interval = T1/2
Cmax/Ctrough ratio =
2
Dosing interval
Dosing interval > T1/2
Cmax/Ctrough ratio =
> 2
Equation to adjust a dosage regimen
New Rate = Old Rate * (Desired Css/Measured Css)
What kinds of drugs are especially important to monitor
Marked PK variability
Narrow Safety Margins
Therapeutic/Adverse effects related to drug conc.
Difficulty monitoring for desired therapeutic effect
