BIOE 425/625

Spring 2004

Homework 1

Due  Feb 5, 2004

 

Topics:  One compartment pharmacokinetic modeling for intravenous dosing, with renal excretion,  liver metabolism and urine analysis .  Each problem is worth 20 pts

 

 

 

1.  Penicillin G is unstable in the gastrointestinal tract because  the b-lactam is subject to hydrolysis to form penicilloic acid, 

                                                hydrolysis

                        Penicillin                 g    penicilloic acid

 

This hydrolysis leads to a decrease in potency of the drug, especially in gastric acid. Therefore it is usually orally dosed on an empty stomach or via IV injection ( unlike Augmenten that is dosed with food to decrease stomach upset or Griseofulvin that is given with a fatty meal to increase bioabsorption).

. 

 The rate loss of penicillin has been observed to be 1st order in dilute solutions of acid.    The following data has been obtained for a dilute solution of penicillin at pH 1.3 and 37 C.  Draw the concentration profile.  What is the value of the first order rate constant? Use any software you would like

 

Time (hr)

Concentration (x 102 M)

0.0

9.00

1.0

7.40

2.0

6.05

3.0

5.00

4.0

4.08

5.0

3.34

6.0

2.75

7.0

2.25

8.0

1.85

10.0

1.25

24.0

0

 

 

 

 

 

 

2.  A patient is to be started on two medications (A and B) administered by IV bolus

injections on a monthly basis. Blood samples were taken 1 and 4 hours following the

first injections in order to determine whether concentrations were in an appropriate

range for each drug. See table below for these levels and additional information. Fhep

and Fren are the fractions of total clearance (CL) due to hepatic and renal processes, respectively.  See the attached article Clearance of drugs by the kidney’s if you need more info on elimination processes.

 

Drug    Dose (mg)       Cp at 1 h (mg/L)          Cp at 4 h (mg/L)         Fhep    Fren

A         400                 1.22                             0.76                              0.1      0.9

B         1200                0.92                            0.51                             0.6      0.4

 

Assume liver blood flow of 90 L/hr, renal blood flow of 66 L/hr and glomerular filtration rate GFR of 130mL/min (7.8 L/hr). Calculate the following for both drugs A and B (a-e are worth 3 pts each and f is worth 5 points)

(a) t1/2

(b) Vd

(c) CL

(d) hepatic clearance rate

(e) renal clearance rate

(f) Explain (in words) what each answer means and compare the two drugs.

 

 

 

3.   Contrast media was injected into the right renal artery containing 2 mg of dye.   The following concentration data was obtained from the right renal vein and corrected for recirculation.  Renal blood flow is assumed constant.  Using these data to estimate the area under the dye curve using the  trapezoidal rule and Simpson's rule (1/3 or 3/8).  Which method has the least error associated with it?

 

Show your work.

Time (sec)

Concentration (mg/L)

3

1.0

4

10.0

5

25.0

6

15.0

7

3.0

8

2.0

9

1.0

 

 

 

 

 

 

 

 

4  Cocaine is known to follow one-compartmental model pharmacokinetics.  After 30 mg is administered as a single I.V. bolus dose, the following data were observed:

Time (hr)

Conc (mg/l)

0.5

0.1213

1

0.073

2

0.0271

3

0.0100
  1. Plot it (semi log)
  2. Calculate the half life  and elimination rate constant
  3. Calculate the initial plasma concentration Co
  4. Calculate the volume of distribution given the body weight of the subject is 75 kg
  5. Calculate the amount of drug in the body at 4 hours
  6. Calculate the total AUC using numerical methods (to t= infinity)

 

 

5.  Read Ciprofloxacin absorption paper by Harder et. al (passed out in class and available on webpage).  Write a summary ( < 1 page) of their study.   You should be able to give an overview of their work (purpose, experiential procedure, findings)  and point out the strengths and weaknesses of their research.   Don’t just rewrite the abstract.