One Compartment Model Flashcards by Anna Van Dekerkhove

What is the goal of pharmacokinetics?

Quantitative account for the amount of drug entering and leaving the body

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What is clinical pharmacokinetics?

Application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual px

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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

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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

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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)

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Will the same dose of a drug produce the same peak plasma [drug]?

No, one dose can produce a high variability in [drug]

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What are the components of therapeutic drug monitoring?

Assay of [drug] plasma

- Interpretation and application

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Which drugs are commonly monitored?

Aminoglycosides
Antidepressants
Cyclosporin
Methotrexate
Valproic acid

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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

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When is therapeutic drug monitoring not appropriate?

No defined therapeutic [drug]
Active metabolite
Toxic reactions may occur at all [drug]

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What is assumed w/ the one compartment model?

Instantaneous distribution to whole body

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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)

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What is considered the central compartment?

Heart
Liver
Lungs
Kidney
Blood

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What is considered the peripheral compartment?

Fat tissue
Muscle tissue
Cerebrospinal fluid

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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

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Can the same drug have a different k value?

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Can 2 different drugs have the same k values?

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What is the initial equation of the one compartment model?

dCb/dt = -KCb

- Cb = concentration in blood

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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

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What is the formula to find t1/2 from k for first order?

t1/2 = 0.693/k

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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)