1. Complete the following statements for a low molecular weight drug which does not bind to plasma proteins.…
(10 points)

A. The maximum value which renal clearance can approach that of

..........................................................................................

B. If this drug is hydrophilic and not interacting with transporters the largest possible renal clearance is that of

..........................................................................................

C. If this drug is lipophilic, neutral drug and not interacting with transporters the smallest possible renal clearance is that of

..........................................................................................

D. Assuming that the lipophilic drug is a base, renal clearance can be reduced by…

..........................................................................................

2. Consider the two drugs A and B. Drug A shows perfusion limited distribution into the brain. Drug B is entering the brain characterized by permeability limited distribution. List the statements in agreement with this observation (10 points).

a) Drug A might be more lipophilic than drug B.

b) Drug A will enter the brain faster than drug B.

c) Drug A might be a stronger base than drug B.

d) Drug B might be a stronger base than drug A.

e) Drug B will enter the brain faster if blood flow through the brain is increased.

f) Drug A will enter the brain faster if blood flow through the brain is increased.

List correct statement(s):

..........................................................................................

3. Choose whether the following statements for a high extraction drug are True or False
(10 points)

or The volume of distribution has to be small

or A decrease in liver blood flow will increase oral bioavailability

or An increase in intrinsic clearance, due to enzyme induction will increase hepatic clearance

or An increase in plasma protein binding will decrease clearance

or Oral bioavailability is increased with increased liver blood flow

For the following relationships, draw a line that best describes the relationship between the two parameters. If no relationship exists, write "N/R". (15 points)

Move Mouse Over Graph to See Answer

A)	B)
C)	D)

5. For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic, unionizable (no acid or basic group in the molecule), protein bound drug that shows extensive liver metabolism (E=1) and renal elimination. (some answers may be used more than once). (15 points)

Physiological change Effect on kinetics

6. For the following situations, indicate whether the drug is filtered, reabsorbed or actively secreted (Assume GFR is 130 mL min^-1, urine flow is 1.5 ml min^-1) (15 points)

• A drug with f_u = 0.01 and a Cl_REN = 20 mL min^-1 is _______________________
• A drug with f_u = 0.50 and a Cl_REN = 65 mL min^-1 is _______________________

• A drug with f_u = 0.20 and a Cl_REN = 0.3 mL min^-1 is _______________________

7. A drug is eliminated through glomerular filtration and hepatic metabolism. It does not bind to plasma proteins. Glomerular filtration rate is normal. No active renal secretion and passive or active reabsorption after renal filtration is observed. The volume of distribution is 50 L. When given as an i.v. bolus, plasma concentrations one hour after administration were 5.2 mg/L. 3 hours after administration the concentration was 2.6 mg/L. (25 pts)

a. What is the plasma concentration 8 hours after administration of the drug?

Answer

b. What is the hepatic clearance?

Answer

 

Answers .pdf format