PHA 5127

First Exam

Fall 2002

1.      True or False  The oral bioavailability of a drug whose clearance is close to the liver blood flow  (15 points)

T         F            will be small

T       F              will depend on liver blood flow

T        F            will depend on plasma protein binding

T         F             will be close to 100%.

T         F            will be affected by the GFR

2.      Compare the following two concentration time profiles  (15 points).

The 2 graphs differ in either

Dose,

Vd

Clearance

Give the reasons for your decision

 

3.      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
1.)  Increase in metabolic enzymes Click to see answer
2.) Decrease in urine flow Click to see answer
3.)   Increase in liver blood flow Click to see answer
4.) Decrease in number of fat cells Click to see answer
5.)  Decrease in creatinine clearance Click to see answer

 

4.      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)

Fill in the blank

A drug with fu = 0.02and a ClREN = 20  mL min-1 is

 A drug with fu = 0.40 and a ClREN = 52 mL min-1 is

 A drug with fu = 0.30 and a ClREN = 0.45 mL min-1 is

5.      A drug is eliminated through glomerular filtration and hepatic metabolism (no other clearance mechanisms are observed). It does not bind to plasma proteins. Glomerular filtration rate is normal (130 ml/min).  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)

5a.       What is ke?

5b.  What is the total clearance of the drug.

5c. What is the renal clearance of the drug?

5d.    What is the hepatic clearance of the drug?

5e.    After 10 doses of this drug (given once a day) the concentration two hours after the last dose is 3.67 mg/L. What will be the concentration 10 hours later (12  hours after the last injection)

 

6.         The same dose of Alprazolam was given either alone or with ketocozanole.  Explain what is going on. (15 points)

 

Answer for printing