Clinical Pharmacokinetics

Dr. Scott
4/12/2012 Exam #3

K.J. is a 65 year-old white male admitted to the hospital two days ago.
CC: Fever, dyspnea, fatigue, productive cough, swelling in hands and feet as well as nasal and
chest congestion.
HPI: K.J. was fine until about five days ago when he began to feel excessively fatigued, and
weak. He contributed these symptoms to a cold or allergies
PMH: Hypertension, Diabetes, Hyperlipidemia, Asthma, Cystic Fibrosis and newly diagnosed
CHF
Home Meds: Lasix 40mg poqd, Vasotec5mg poqd, ADVAIR 500/50 -1 puff bid, Aspirin
325mg qd, Pepto-bismol 30ml q6h prn, and Ventolin MDI 2 puffs qidprn
PE: BP 189/106, HR 102, Temp 102, RR 12, ht. 59; wt205 lbs. Patient appears well
hydrated and in good spirit. Stools are dark, tarry and heme positive. Also CXR revealed
LLL infiltrate.
Admitting Labs: SrCr 1.3mg/dL, BUN 40mg/dl, Na 140meq/L, K 5.4meq/L, glucose 107mg/dl, Phenytoin
3mg/L, Ca++ 7.9meq/L, WBC 13,000, and albumin 2.0gm/dL.
Assessment/plan
1. Possible Pneumonia
2. Possible Dehydration
3. Start Tobramycin 140mg q8h

Questions: Must show all work/calculations when necessary in order to receive credit
1. Which of the following is true?
a. Patient is experiencing GI bleed
b. Patient is experiencing Dehydration
c. Patient is experiencing Stroke
d. A and B only
e. All of the above

2. Which of the following factors can affect the disposition of drugs used in this case?
a. Cystic Fibrosis
b. Renal function
c. CHF
d. All of the above
e. A and C only

3. Patients on dialysis will require a vancomycin dose approximately 3 times normal dose because
aminoglycosides will be lost (concentration drastically reduced) during the process.
a. True
b. False

4. Which of the following factors associated with this case could result in an increase pharmacodynamic
response to Coumadin, due to an alteration in the pharmacokinetics of Coumadin.
a. Aspirin
b. Pepto-bismal
c. Albumin level
d. A and C only
e. All of the above


5. Do you agree or disagree with the dose of Tobramycin ordered by the physician? Very briefly explain your
reasoning.

70.7kg Cmax = 140mg * (1-e
-0.1923
) = 9.18mg/L
Vd=17.675 L 3.399 L/h * (1-e
-0.1923 *8
)
CL=3.399
k = 0.1923 Cmin = 9.18 * e
-0.1923(7)
= 2.389mg/L
Tau = 8 hr


I disagree because trough (2.389mg/L) is too high


6. If you disagree calculate a Tobramycin dose that will maintain a peak of 8mg/L and a trough of <2mg/L.


new T = [ ln (2/8) *
-
1 ]
+ 1
= 8.209 12hr
0.092346

D= Cmax desired (8mg/L) * 3.399 L/h * (1-e
-0.1923*12
) =
(1-e
-0.1923
)

D = 139.97mg q12hr


7. The patient has been receiving the dose of Tobramycin 140mg q8 for the past 3 days (at 8am, 4pm, and
12am). The concentrations were taken on 4/11 @ 7:58 am and on 4/11 @ 11:02 am. The 11:02
concentration was 6.86mg/L and the 7:58 concentration was 0.6mg/L. Based on this information should the
physician continue this dose?

k = ln (0.6/6.86)*
-
1 = 0.4873 Cmax = 6.86mg/L = 18..1797mg/L
5 e
-
0.4873(2)


Do not continue because peak (18.18mg/L) which is too high for conventional
dosing.

8. The physician Decided to place K.J. on once a day dosing. Calculate a dose of Tobramycin that will
maintain a peak of 20mg/L and a trough <2mg/L.


CL = 140mg * (1-e
-
0.4873
) = 3.03 L/hr
18.1797mg/L * (1-e
-
0.4873*8
)

T = 24hr

D = 157.12mg q24hr D= Cmax desired (20mg/L) * 3.03L/h * (1-e
-
0.4873*24
) =
(1-e
-
0.4873
)



9. Gentamicin and Tobramycin have the ability to kill gram + organisms such as Staphylococci(MRSA) when
given with vancomycin.
a. True
b. False

10. When an aminoglycoside (i.e. tobramycin) is given with vancomycin, the pharmacodynamics response of
vancomycin increases against MRSA because
a. Aminoglycosides displace vancomycin from protein binding sites.
b. Aminoglycosides decrease the clearance of vancomycin, thus causing the concentration to increase.
c. Aminoglycosides and vancomycinis said to have a synergistic effect; however, they do not have an
effect on the same organisms and have different spectrum of antibiotic activity
d. B and C only
e. None of the aboave


11. The physician wants to start vacomycin at a dose 500mg q6h, do you agree or disagree with the physicians
dose?

70.7kg Cmax = 500mg * (1-e
-
0.044642851
) = 42.049mg/L
Vd = 49.49 L 2.2093747 L/h * (1-e
-
0.044642851*6
)
CL = 2.2093747
k = 0.044642851 Cmin = 42.049 * e
-
0.044642851(5)
= 33.64mg/L
Tau = 6hr


I disagree because peak (42.049mg/L) and trough (33.64mg/L) are both too high


12. If you disagree calculate a vancomycin dose that will maintain a Peak of 30mg/L and a trough of 6.3mg/L.


new T = [ ln (6.3/30) *
-
1 ]
+ 1
= 35.9 36hr
0.044642851

D= Cmax desired (30mg/L) * 2.2093747L/h * (1-e
-
0.044642851*36
) =
(1-e
-
0.044642851
)

D = 1213.77mg q36hr













13. The physician wants to start a continuous infusion of aminophylline that will maintain a theophylline
concentration of 15mg/L. Calculate the continuous infusion dose.

CL = 70.7 * 0.04 = 2.828 L/h
D = 2.828 L/h*15mg/L*1h=
53.025 mg/hr
0.8

14. The physician decided to use a continuous infusion dose of 75mg/hr. Based on this continuous infusion
dose of aminophylline, what will the concentration be 15 hours after the start of the continuous infusion?

Cp = 75mg*0.8*1
*
1-e
-0.08 (15)
= 14.826 mg/L
2.828 L/hr *1hr

15. Because the steady state concentration of Theophylline was 25mg/L at the current dose of aminophylline,
the physician decided to stop the infusion. How long will it take for the concentration to drop 15mg/L?

CL = 75mg*0.8*1= 2.4 L/hK = 2.4 L/h = 0.0678925
25mg/L 35.35
t = ln (15/25) *
-
1 =
7.52 hr
0.0678925
note: if you continued using 0.08 as your k credit was given this time; however
for future reference calculate individualized CL. t= 6.385h

16. The steady state concentration of Theophylline was 25mg/L at 8pm using the current dosing information,
thus the physician decided to stop the infusion. If the physician decided to recheck the concentration at 8am
what would the concentration be at that time?

C = 75mg*0.8*1
*
e
-0.0678925 (12)
=
11.07mg/L
2.4 L/h
note: if you continued using 0.08 as your k credit was given this time; however
for future reference calculate individualized CL. C =9.57h

17. If the concentration from question is less than 10mg/L, calculate an aminophylline LD that achieve a
concentration of 15mg/L.

note: if you continued using 0.08 as your k credit was given this time; however
for future reference calculate individualized CL. LD= 239.84mg
Concentration > than 10mg/L no Calculations required

K.J. has a theophylline concentration of 25mg/L at 8pm and at 8 hours later he had a serum concentration of
14.52mg/L. K = ln(14.52/25) = 0.067919
-
h
8
18. From the information given calculate the half-life of theophylline for this patient.
t
1/2
= 0.693/0.067919

h =
10.2 hr

19. From the information given calculate at what time was the second concentration taken.

4am
20. Also determine, what is the minimum amount of time needed for the drug to reach steady state in this
patient?
10.2 * 5 = 51hr
21. If Drug X has a distribution half-life of 0.2 hours and an elimination half-life of 23 hours. If A = 40 and B =
30mg/L. What will the Drug X plasma concentration be 12 hour after the infusion?

20.898mg/L
Cp = 40mg
*
e
-3.465 (12)
+
50mg
*
e
-0.03013 (12)


22. Using the information in question #21, how much Drug X will accumulate if 750mg was given q48 hours.
ACC = 750mg
980mg
1-e
-0.03013 (48)
=

23. Which of the following factors will decrease bioavailabilty?
a. first pass effect
b. GI motility
c. Salt Form of the drug
d. B and C only
e. None of the above
f. All of the above

24. Nephrons excretes drugs from by the body which of the following processes?
I. glomerular filtration
II. tubular secretion
III. tubular reabsorption
a. I only
b. I and II only
c. I and III only
d. I, II, and III
e. none of the above

Assuming a patient has received IV loading dose of Drug X 1000mg. Immediatelyafter the dose was given the
concentration was 25mg/L and 22 hours after the dose was given the concentration was 2mg/L. When given
orally drug X is 95% metabolized via first past effect. (Use this information for questions 25-27)

25. Base on the information directly above, what is the elimination rate constant of Drug X?

k = ln (2/25)*
-
1 =
0.114806 -h
22

26. Base on the information directly above, what is the half life of Drug X?

t
1/2
= 0.693/0.067919

h =
6.036585 -h

27. Base on the information directly above, what is the clearance of Drug X?

VD = 1000mg = 40 L CL = 40 L * 0.114806 =
4.592L/h
25


28. Write out the equation for adjusted dosing weight and give the range for the correction factors

ADW = IBW + CF (ABW IBW) CF = 0.1 0.4




29. Which of the following is true in Zero Order Kinetics
a. Amount of drug eliminated at a set time is constant, regardless of the amount of drug in the body.
b. Fraction or percent eliminated does not vary.
c. Non-linear
d. All of the above are true
e. A and C only are true

30. Ionized drugs are completely inhibited from crossing the cell or plasma membrane and will never cross?
a. True
b. False