PHA 5127

Basic Principles of Dose Optimization

(formerly)

PHA 4120- Biopharmaceutics and Pharmaceutics

Practice Exam
Given as Final Fall 1995

The entire exam with the answers can be printed with Adobe Acrobate Reader. Final95.pdf

 

1. Mark whether the following statements concerning oral bioequivalence are true (T) or false (F). (8 pts)

Cpmax and tmax are sufficient to assess bioequivalency

AUC does not have to be considered

The dissolution rate of the drug in the GI tract is not important

Sustained release products do not need to be tested, since bioequivalence is not a problem for this dosing form.

2. Select the correct answer(s). Consider linear pharmacokinetics. The metabolic clearance of a lipophilic, neutral, high extraction drug after oral administration is significantly affected by: (8 pts)

The dose

The plasma protein binding

The tissue protein binding

The pH of the G.I. tract
COMMENT: For a high extraction drug, the hepatic clearance depends only on liver blood flow.

3. Aminoglycosides are predominantly eliminated via glomerular filtration. You have a patient with a creatinine clearance of 30ml/min. The volume of distribution is identical to the population average. What dosing regimen would you identify as the most optimal one when compared to the one of a patient with normal with normal creatinine clearance of 125 ml/min. (8 pts)

Reduce each dose by half and double the dosing interval

Reduce each dose by half and shorten the dosing interval by half

Reduce each dose by half and use the same dosing interval

None of the above

4. Which of the following factors might affect the renal clearance of a drug: Assume the drug is only cleared by glomerular filtration. (5 pts)

Pregnancy

Protein binding Comment: only free drug is filtered

Lipid solubility

Degree of ionization Comment: ions filtered too

Liver blood flow Comment: not important at all for renal function

The correct answer is

5.Which of the following event(s) will increase the volume of distribution in a patient. (8 pts)

Increase in clearance of the drug


Increase in the fraction bound in the tissue


Increase in the fraction unbound in plasma


Increase in the dose

The answer is

6. Select for the following pharmacokinetic phenomena, the relevant optical representation. (10 pts)

 

a) IV bolus injections of a drug with saturable renal reabsorption
Click on button to chose answer

Comment:drug is still filtered – Cl increases with sat’d reabsorption

b) IV bolus injection of a drug which shows with saturable G.I. absorption
Click on button to chose answer

Comment: no absorption for i.v. administration

c) Transdermal absorption by active transport
Click on button to chose answer

Comment: active transport can be saturated

d) High extraction drug with saturable plasma protein binding
Click on button to chose answer

Comment: ClH is independent of protein binding for a high extr. drug

e) Low extraction drug with saturable enzyme kinetics
Click on button to chose answer

Comment: ClH = Clint× fu. If Clint is small then ClH is low. Increasing dose causes a disproportional increase in AUC during the saturation.

7. The following concentration time profiles were observed. The two curves differ in one of the input parameters (Dose, Tau, CL or Vd). Identify the parameter which differs. (5 pts)

8. A 23 year old female, Patient MS (60 kg), is receiving IV bolus injections of theophylline. The dose is 200 mg every 6 hr with satisfactory response. Recently, steady state theophylline plasma concentrations were determined to be 15 mg/L, 1 hour after the last dose administration and 8.2 mg/L 6 hr after the last dose administration (trough). (20 pts)

a) Determine the elimination rate constant.

b) Determine the volume of distribution (Remember: C0=D/Vd, you might have to substitute this into another equation).

c) Determine the clearance.

d) Estimate also the average steady state theophylline concentration (Cpss) with this regimen.

9. A patient has a total body weight of 75.34 kg, equivalent to an IBW (ideal body weight) of 52.3 kg. The elimination rate constant based on population parameters is 0.146 hr-1. Prior to surgery, you are asked to begin this patient on an aminoglycoside therapy. The drug will be administered by intravenous, intermittent infusion over one hour. The volume of distribution is be 0.24 L/ kg of ideal body weight. (20 pts)

Calculate an appropriate aminoglycoside maintenance dose, including the most appropriate dosing interval to achieve a desired Cpeak of 6 mg/L and a Ctrough of 1 mg/L.

10. List the main advantage of the statistical moment theory, compared to the compartmental approach in not more than two sentences. (10 pts)

11. The concentration-time profile of two drugs (A and B) exhibit a two compartment body model. Drug A shows serious toxic effects immediately when plasma concentrations exceed 20 mg/ml while B shows side effects if levels exceed 20 mg/ml over a time period of 10 minutes. One compartment body model equations are often used in clinical pharmacokinetics even if the drug shows two compartment body model behavior. (20 pts)

12. A hydrophilic drug needs to be dosed in an overweight patient (200 lbs). In a patient with IBW (120 lbs) the dose is 200 mg every 6 hours. How would you dose the overweight patient? (10pts)

.

Return to PHA 5127 Syllabus