PHARMACOKINETICS PROBLEMS

  1. Assuming first order kinetics what fraction of an IV drug dose remains in the body after 4 half-lives?
  2. The t1/2 of a drug is 6 hours. What fraction is left in the body at 21h post drug administration?
  3. Twenty percent of a drug dose remains in the body at t=10hours. What is the half-life of the drug?
  4. The plasma concentration of a drug administered by IV bolus injection may be described by the following equation:

Ct = 0.92e -0.35t

where Ct is in units of mg/L and the time (t) is in hours.

If the dose is 50mg calculate the following:

  • The plasma concentration at 6.5h post dosing.
  • The plasma half-life.
  • The volume of distribution.
  • The area under the plasma concentration versus time curve.
  • The total clearance.

 

  1. Drug X is administered as an IV bolus dose of 100mg and the following plasma concentrations were obtained with time:
Time (h) 0.25 0.5 1.0 3.0 5.0 7.0 10.0
Plasma Concentration (mg/L) 2.6 2.4 2.1 1.2 0.75 0.45 0.2

Calculate the volume of distribution, plasma half-life and clearance of X.

X was subsequently administered via the oral route at a dose of 200mg as both an aqueous solution and as a formulated product. The measured areas under the plasma concentration time curves were 14.3 mg/L.h and 12.6 mg/L.h for the solution dose and formulated product respectively.

 

Using this data calculate the relative and absolute bioavailability of X.

  1. Drug W on IV administration to an experimental animal at a dose of 10mg/kg (animal weight 2.3kg) gave the following plasma concentrations with time:
Time (h) 0.1 0.25 0.5 0.75 1.0 1,5 2.0 3.0 4.0
Plasma Concentration

(mg/L)

4.2 3.2 2.3 1.8 1.5 1.2 1.09 0.88 0.71

 

Using the above data:

  • Draw a diagram of a compartmental model that describes the plasma disposition of the drug and indicate any relevant rate constants.
  • Write an equation describing the plasma concentration versus time curve (use numbers rather than symbols as much as possible).
  • Calculate the values of the rate constants you have indicated in part (a).
  • What is the terminal half-life of drug W?
  • What is the volume of distribution of W and what is the initial dilution volume (volume of the central compartment)?
  • Calculate the area under the plasma concentration versus time curve and compare this value with that obtained using the trapezoidal method.

 

  1. Drug Y is administered orally to a patient at a dose of 100mg and the following plasma concentrations were obtained with time:
Time (h) 0.2 0.4 1.0 2.0 3.0 4.0 6.0 8.0 10.0
                   
Plasma Concentration (mg/L) 0.33 1.0 1.8 2.02 2.0 1.6 1.0 0.6 0.38

 

Calculate the absorption and elimination rate constants, the volume of distribution and clearance of Y assuming that F, the bioavailability, is equal to 0.75.

If the 100mg oral dose is repeated at 8 hourly intervals calculate the maximum, minimum and average steady-state plasma concentrations.

  1. Drug A is administered IV to a patient according to the following table:

 

Day Time Dose (mg)
1 4.00pm 80
  11.00pm 160
2 7.00am 120
  1.30pm 80

 

At 4.00pm on day 2 a plasma sample was analysed for A and a concentration of 6mg/L was obtained.

Is this measured concentration consistent with the expected value?

Volume of distribution of A is 14.5L and clearance is 40mL/min.

 

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