a) A and B differ in one primary pharmacokinetic parameter. Discuss the above concentration time profile.

 b)         Why is steady state reached faster in patient A?

2.) True or false

A drug with a long half-life takes a shorter time to reach steady state than a drug with longer half-life.

When developing a multiple dose regimen, doubling both the dosing interval and the dose will result in the same average plasma concentration.

An increase in drug dose will result in higher plasma concentrations at steady state but will not change the time to reach steady state.

If the dosing interval is decreased, the time to reach steady state is reduced. Dependent on t_1/2

Loading doses are administered prior to beginning a continuous intravenous infusion to provide an immediate as well as a sustained effect of the drug.

For rapidly absorbed as well as slowly absorbed drugs, the bioavailable dose is directly related to the AUC.

  The faster the absorption rate of a drug the steeper the terminal slope of the downhill portion of the concentration time profile. K_e independent of ka must assume normal kinetics (albeit this is obvious from the wording of the statement)

  Assume a drug which is mainly eliminated through hepatic metabolism. The area under the concentration time profile after oral administration of such a drug is affected by the hepatic extraction ratio E

For a two-compartment body model drug, the volume of distribution of the central compartment is larger than the volume of distribution at steady state. V_d centreal is smaller prior to distribution. This results in higher, short-lived concentrations just after injection.

5.)   (10 points) Mark the correct statement(s). If  plasma concentrations are determined soon after an intravenous dose is given for a drug that exhibits biexponential elimination and if a one-compartment model (monoexpoential ) is assumed, the  resulting elimination half-life:

Cannot be determined

Might be erroneous

Will underestimate the terminal phase (t_1/2 too short)

Will overestimate the half-life of the terminal phase (t_1/2 too long)

Check answer

6.)          (10 points) The following equation describes the plasma concentration-time profile after multiple dosing of an i.v. bolus injection

This equation can be sub-divided into three functional units.  Each of these units is responsible for a certain pharmacokinetic property of the multiple dosing system. List the meaning (function) of each of the three group-terms

7.)                (20 points) A 60-year old female patient BA (70 kg) is being treated for a hospital-acquired, methicillin-resistant bacteremia.  She was given a 1000 mg vancomycin loading dose and is now receiving 500 mg (infused over one hour) every 12 hours.

 The estimated elimination rate constant for vancomycin (population average) has been calculated to be 0.029 hr^-1. Her volume of distribution is 0.9L/kg  (63L).

Predict the steady state trough concentration C_trough  (just before starting the next infusion) for this dosing regimen.

b) What dosing interval (t) would you recommend to attain a C_peak (real peak directly at the end of infusion) of 25 mg/L and a C_trough (real trough at the beginning of the next infusion) of 7 mg/L (k_e= 0.029 hr^-1)

Cp (ng/ml)

                                                  Time (h)