Pharmacology: Multiple-Dosage Regimens
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Questions and Answers

What is the elimination rate constant (k) for a drug with a half-life of 3 hours?

  • 0.115 hr−1
  • 0.333 hr−1
  • 0.693 hr−1
  • 0.231 hr−1 (correct)

    • In a one-compartment model, the maximum amount of drug in the body after repetitive intravenous injections will always equal the injected dose.

    False

    What are the maximum and minimum amounts of drug in the body after the steady state is reached for the patient receiving 1000 mg every 6 hours?

    Maximum: 1333 mg, Minimum: 333 mg

    The fraction of the drug remaining in the body at the end of each 6-hour interval is equal to _____

    <p>0.25</p> Signup and view all the answers

    Match the following terminology related to drug kinetics:

    <p>Dmax = Maximum drug concentration in the body Dmin = Minimum drug concentration in the body t1/2 = Half-life of the drug ss = Steady state concentration</p> Signup and view all the answers

    What assumption is made about the timing of the next dose in multiple oral dose administration?

    <p>The next dose is given after the absorption phase is complete.</p> Signup and view all the answers

    If ka >> k, then (ka - k) can be approximated as ka.

    <p>True</p> Signup and view all the answers

    What is the equation for Cpmin when ka >> k?

    <p>Cpmin = (Fka D0 / VD) * (e^(-kτ) / (1 - e^(-kτ)))</p> Signup and view all the answers

    In the simplification for Cpmin, assuming ka >> k, the term ka/(ka - k) is approximately equal to ______.

    <p>1</p> Signup and view all the answers

    Match the following terms with their descriptions:

    <p>Cpmin = Minimum plasma concentration ka = Absorption rate constant k = Elimination rate constant VD = Volume of distribution</p> Signup and view all the answers

    What is required for the superposition principle to apply?

    <p>The drug to be eliminated by first-order kinetics</p> Signup and view all the answers

    Doubling the dose will result in a doubling of the drug concentrations at each time point.

    <p>True</p> Signup and view all the answers

    What factors can cause the superposition principle not to apply?

    <p>Changing pathophysiology, saturation of a drug carrier system, enzyme induction, and enzyme inhibition.</p> Signup and view all the answers

    The formula for the accumulation index is __________.

    <p>1/(1 - e^(-KEτ))</p> Signup and view all the answers

    Match the pharmacokinetic terms with their definitions:

    <p>C max = Maximum drug concentration in the bloodstream after a dose C min = Minimum drug concentration in the bloodstream before the next dose Accumulation = Increase in drug concentration due to repeated doses Half-life = Time taken for the drug concentration to reduce by half</p> Signup and view all the answers

    What determines the rise and fall of drug concentration during accumulation?

    <p>The relationship between elimination half-life and dosing interval</p> Signup and view all the answers

    Accumulation of a drug is independent of the size of the dose.

    <p>True</p> Signup and view all the answers

    How does the dosing interval relative to the elimination half-life affect drug accumulation?

    <p>Shorter dosing intervals lead to larger residual amounts of drug and increased accumulation.</p> Signup and view all the answers

    What is the average amount of drug in the body at steady state for intravenous injections?

    <p>F D0 / kτ</p> Signup and view all the answers

    D∞av is the arithmetic mean of D∞max and D∞min.

    <p>False</p> Signup and view all the answers

    What is the formula used to calculate C∞max?

    <p>Dm∞ax / VD(1 - e^(-kτ))</p> Signup and view all the answers

    For this example, the value for C∞max is __________ μg/mL.

    <p>66.7</p> Signup and view all the answers

    How long does it take to reach 90% of steady state plasma concentration?

    <p>3.3 times the elimination half-life</p> Signup and view all the answers

    The time to reach 99% steady state plasma concentration is shorter than the time to reach 90% steady state plasma concentration.

    <p>False</p> Signup and view all the answers

    Match the following values with their respective concentrations:

    <p>C∞max = 66.7 μg/mL C∞min = 16.7 μg/mL C∞av = 36.1 μg/mL D∞av = 720 mg</p> Signup and view all the answers

    What is the relationship between accumulation half-life and elimination half-life?

    <p>Accumulation half-life is directly proportional to elimination half-life.</p> Signup and view all the answers

    What is the formula used to determine Dmax?

    <p>D0 / (1 - f)</p> Signup and view all the answers

    The maximum concentration of drug in the body decreases over time due to zero-order drug elimination.

    <p>False</p> Signup and view all the answers

    The maximum amount of drug in the body after a single rapid IV injection is equal to the ________ of the drug.

    <p>dose</p> Signup and view all the answers

    Which of the following factors affects the time required to reach steady state during multiple constant dosing?

    <p>Elimination half-life</p> Signup and view all the answers

    What is D av when F is set to 1 and D0 is set to 1000 mg with k = 1.44 and τ equal to 3?

    <p>720 mg</p> Signup and view all the answers

    Match the drug dosage intervals with their corresponding drug amounts remaining in the body after successive doses:

    <p>τ = t1/2 = 75 mg D0 = 100 mg after 1st t1/2 = 50 mg After 2nd dose = 150 mg After 2nd t1/2 = 75 mg</p> Signup and view all the answers

    What accumulates when consuming whiskey every hour according to the metabolism rate provided?

    <p>4 gm of ethanol per hour</p> Signup and view all the answers

    If τ is large, the fraction of the drug remaining in the body will be larger.

    <p>False</p> Signup and view all the answers

    Which of the following factors influences the mean plasma drug concentration at steady state?

    <p>Both AUC and τ</p> Signup and view all the answers

    At steady state, the equation for plasma drug concentration can be simplified to reflect a constant concentration after multiple doses.

    <p>True</p> Signup and view all the answers

    What formula is used to determine the plasma drug concentration after multiple doses of a drug?

    <p>CP = D/Vd * (1 - e^(-nkτ)) * e^(-kt)</p> Signup and view all the answers

    The steady-state concentration at time t after the last dose is denoted as C __________.

    <p>P∞</p> Signup and view all the answers

    In the provided example, what was the elimination half-life of the drug?

    <p>3 hours</p> Signup and view all the answers

    The apparent volume of distribution (Vd) mentioned in the example was 30 L.

    <p>False</p> Signup and view all the answers

    Calculate the value of C∞max if 1000 mg of medication is given every 6 hours with a volume of distribution of 20 L.

    <p>66.7 mg/L</p> Signup and view all the answers

    Study Notes

    Multiple-Dosage Regimens

    • Multiple-dosage regimens are used to maintain prolonged therapeutic activity.
    • After a single dose, plasma drug levels rise and then fall below the minimum effective concentration (MEC), leading to a reduced therapeutic effect.
    • In calculating a multi-dose regimen, the target plasma drug concentration must be correlated with a therapeutic response.
    • The regimen must aim to produce plasma concentrations within the therapeutic window, avoiding excessive fluctuations and accumulation outside the window.

    Parameters of Multidose Regimen

    • The size of the drug dose and the frequency (time interval) of administration can be adjusted.
    • The frequency of administration of a drug in a particular dose is called the dosage regimen.
    • The plasma levels of drugs given in divided doses must be maintained within the therapeutic window.
    • The regimen aims to provide the correct plasma level, without excessive fluctuations, keeping drug accumulation outside the therapeutic window.

    Drug Accumulation

    • When a drug is administered at regular intervals, the rise and fall of drug concentration in blood depend on the relationship between the elimination half-life and the time interval between doses.
    • If the drug amount administered in each dose has been eliminated before the next dose is applied, similar plasma levels will result during repeated intake at constant intervals.
    • If intake occurs before the preceding dose has not been eliminated completely, the drug accumulates.
    • The shorter the dosing interval relative to the elimination half-life, the more extensive the accumulation in the body.
    • At a given dosing frequency, accumulation does not continue infinitely but reaches a steady state (Css) where drug intake and elimination are equal.
    • The activity of elimination processes is concentration-dependent, so higher concentrations lead to more rapid elimination.

    Time to Reach Steady State

    • The time required to reach steady state is dependent on the elimination half-life of the drug and the dosing interval, but independent of the dose size or the number of doses.
    • The method for calculating the time to reach a certain percentage of steady-state (for example, 90% or 99%) is described in texts.

    Repetitive Intravenous Injections

    • The maximum amount of drug in the body following a rapid IV injection is equal to the dose.
    • Drug elimination follows first-order kinetics in a one-compartment open model.
    • The amount of drug remaining in the body after several hours can be determined with a simple equation relating dosage interval, elimination constant, and initial dose.
    • A consistent fraction of the dose remains in the body after the dosage interval, leading to an increasing amount of drug which is not fully cleared until a steady state.
    • To reach steady state is depends on the drug's elimination half-life and the dose interval but does not depends on the number of doses.

    Multiple Oral Dose Administration

    • Calculating plasma concentration after repetitive oral doses is more complex.
    • The plasma concentration-time curve after repeated doses has fluctuations. It depends upon the elimination half-life and absorption rate constant and can vary by several factors which are noted.
    • The equation for calculating the average plasma concentration at steady state involves the area under the plasma concentration-time curve (AUC) during the dosing interval and the dosing interval length .
    • For oral administration, absorption and elimination need to be considered. Steady state (Css) is where elimination rate and intake rate of drug are equal and the maximum total drug amount in body is reached.

    Loading and Maintenance Doses

    • Loading doses are used to rapidly achieve therapeutically active plasma concentrations.
    • Maintenance doses are given to sustain those concentrations.
    • Loading doses depend on the volume of distribution and the fraction of the dose absorbed and can differ in one compartment models and multiple compartment models.
    • Steady-state concentration will be reached after several loading and maintenance doses.

    Distinguishing Between Normal and Flip-Flop Kinetics

    • IV bolus data is necessary.
    • The slopes of the terminal lines are a key indicator.

    Superposition Principle

    • It holds when all pharmacokinetic processes are linear or of first order (distribution, metabolism, and excretion).
    • It allows calculating concentrations after several doses by summing the concentrations from each dose.
    • Simple formulas show that doubling the dose doubles the concentration at each dosage interval.

    Non-Uniform Dosing Intervals

    • If dosing intervals are not uniform, calculations will differ.
    • The model can be adapted to account for irregular dosing practices to establish drug concentrations in the body at different dosing times.

    Example and Solutions

    • Methods for calculating drug concentrations and accumulation are demonstrated through example problems, such as determining concentration at various dosing times and during steady states.

    Homework

    • Homework questions related to drug accumulation and relevant pharmacokinetic concepts are listed.

    References

    • Authors and titles of texts used are cited.

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    Related Documents

    Multidosage Regimen PDF

    Description

    Explore the essential concepts of multiple-dosage regimens in pharmacology. This quiz covers the calculations for maintaining therapeutic drug levels and the importance of dosage frequency. Test your understanding of plasma drug concentrations and therapeutic windows.

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