One Compartment Model Flashcards
What is the goal of pharmacokinetics?
Quantitative account for the amount of drug entering and leaving the body
What is clinical pharmacokinetics?
Application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual px
Where is the ideal spot to take a drug sample? What is the problem with this? Where do you take a sample instead?
- Ideal spot = drug in tissue b/c that’s where receptors are (so will tell you how much free drug there is)
- Can’t take a biopsy of tissue just to see drug concentration
- Take sample of drug in blood instead
What is the relationship between [drug] in plasma and [drug] in tissue? When will this relationship not occur?
- Direct relationship, high [drug] in plasma (as free form) means high [drug] in tissue
- This relationship will not occur if there is an active metabolite or if tissue is concentrating the drug
Why is a log dose curve sigmoidal shaped?
- Each drug has a therapeutic window, in which effect will increase relative to dose increase
- Top is flat b/c receptors become saturated, so there is no more response or the organism has died from toxicity (overdose)
Will the same dose of a drug produce the same peak plasma [drug]?
No, one dose can produce a high variability in [drug]
What are the components of therapeutic drug monitoring?
- Assay of [drug] plasma
- Interpretation and application
Which drugs are commonly monitored?
- Aminoglycosides
- Antidepressants
- Cyclosporin
- Methotrexate
- Valproic acid
When is therapeutic drug monitoring valuable?
- Good correlation exists for response vs [drug]
- Wide intersubject variation
- Narrow therapeutic index
- Desired effect cannot otherwise be assessed
When is therapeutic drug monitoring not appropriate?
- No defined therapeutic [drug]
- Active metabolite
- Toxic reactions may occur at all [drug]
What is assumed w/ the one compartment model?
Instantaneous distribution to whole body
What is the two compartment model?
- Immediately after administration drug circulates to highly perfused areas
- After distributive eq’m drug reaches whole body (low perfused areas)
What is considered the central compartment?
- Heart
- Liver
- Lungs
- Kidney
- Blood
What is considered the peripheral compartment?
- Fat tissue
- Muscle tissue
- Cerebrospinal fluid
What is the difference between an IV bolus and IV infusion?
- Bolus = administered through a needle, taking a few minutes to administer
- Infusion = drug is diluted in an infusion bag and is slowly administered, usually taking longer than a few minutes
- W/ bolus, Cmax occurs directly after administration; w/ infusion, [drug] slowly builds up
Can the same drug have a different k value?
No
Can 2 different drugs have the same k values?
No
What is the initial equation of the one compartment model?
dCb/dt = -KCb
- Cb = concentration in blood
What happens if data for a one compartment model is curved on a log scale?
- Can’t do linear regression b/c will be wrong
- Those data aren’t a one compartment model
What is the formula to find t1/2 from k for first order?
t1/2 = 0.693/k
What is the formula to find t1/2 from zero-order?
t1/2 = 0.5Db/ko
What is the formula for Vd using the one compartment open model?
Vd = dose/Cpo
What is the formula for Vd using the model-independent approach?
Vd = dose/K * [AUC]o infinity
What is the Vd of nortriptyline?
1200 L
What is the Vd of digoxin?
600 L
What is the Vd of propranolol?
250 L
What is the Vd of lidocaine?
125 L
What is the Vd of phenytoin?
40 L
What is the Vd of theophylline?
30 L
What is the Vd of gentamicin?
18 L
What is the Vd of cefazolin?
8 L
What is the lowest possible Vd of a drug?
Only distributing to the plasma fluid, which makes up 4% of body weight
What will the [drug] vs time curve look like for an IV dose?
Time 0 will be 100% [drug] and will decrease from there in a curved line
What will the [drug] vs time curve look like for an oral dose?
Time 0 will be 0% [drug] and will increase to a peak and then decrease
What will the log[drug] vs time curve look like?
Straight line, w/ time 0 being the Cmax
What is the formula to find K from slope? What is the special rule for this?
slope = -K/2.303
- This formula only works for log[drug] vs time (post absorption)W curves
What is the difference between the absorption phase and the elimination phase?
- Absorption phase = portion of a [drug] vs time curve that is before Cmax
- Elimination phase = portion of a [drug] vs time curve that is after Cmax
How do you determine the AUC to infinity?
Last [drug] value multiplied by K, then add this value to the total AUC
Can a protein bound drug bind to a receptor?
No, it must dissociate into the free form to get to the receptor
What should be done for a drug w/ a narrow therapeutic index?
Should be monitored w/ blood samples to see where the [drug] is and make sure it is in the therapeutic window
What is critical to know about assays?
Want to do a specific assay so we know what info we’re getting and what we’re assaying (protein-bound, total, free, etc.)
What do we care about w/ respect to the 2 compartment model?
The eq’m between the 2 compartments
What is K the sum of?
All the different types of elimination (excretion, metabolism, etc.)
What should be done in an emergency when you need drug levels to go up immediately?
Give a bolus and then follow up w/ an infusion to keep blood concentration steady
What assumption is being made when using the rate expression (dCb/dt = -kCb)? What should be done if the drug has a narrow therapeutic index?
- Assuming the px is in the 95% confidence interval
- If they are an outlier, then the calculation would be wrong and the dose would be wrong
- If the drug has a narrow TI, make sure the px is in the 95% interval
What is ko?
The zero-order elimination rate constant
When will Vd change?
If disease state changes
When plotting a graph on log paper, do you plot the actual drug concentration or the log of the drug concentration?
Actual concentration
How do you calculate AUC for 2 data points?
((2nd time point - 1st time point)/2) * (1st [ ] point + 2nd [ ] point)
What is relative availability?
AUCa(drug product) / AUCb (recognized standard)
- If a and b are different doses = (AUCa/dose a)/(AUCb/dose b)
