1. Pharmacokinetics Tutoring
Allie punke, pharmd

2. Multiple Dose Regimens

3. Fluctuation
You are giving a drug with a very narrow therapeutic index. What would be the best regimen to give the smallest degree of fluctuation
2,000 mg QD
1,000 mg BID
500 mg QID
It doesn’t matter—they all have the same degree of fluctuation c

4. Fluctuation
A new drug has two different dosing regimens: 100mg QID or 400mg Qday. Which of the following is true about 100mg QID regimen as compared to the 400mg Qday regimen?
A. Same Css, less fluctuation
B. Different Css, less fluctuation
C. Same Css, more fluctuation
D. Different Css, more fluctuation

5. Fluctuation
Drug A has a half-life of 8 hours and Drug B has a half-life of 15 hours. They are both given at 200 mg QD and have the same bioavailability. Which of the following are true?
Drug A will have a higher degree of fluctuation
Drug B will have a higher degree of fluctuation
Drug A will have more accumulation
Not enough information given

6. Accumulation
Which of the following variables do NOT affect the extent of accumulation?
Dose
Volume
Clearance
Dosing interval a

7. Accumulation
Drug A has an AF of 10. Drug B has an AF of 2. Which of the following would be the best for a patient with a history of non compliance?
A. Drug A
B. Drug B
C. Both will be the same.

8. Effect of ka
Which of the following could be the result of a decrease in ka?
Change in half life
Decrease in fluctuation
Decrease in accumulation
Not enough information

9. Fluctuation
Two different formulations are available for a new oral drug that will be given multiple times during the day . Drug A has a ka value of 1 hr-1. Drug B has a ka value of 0.5 hr-1. Which of the following are true?
A. Drug A will exhibit more fluctuation
B. Drug B will exhibit more fluctuation
C. They will exhibit the same fluctuation, since ka doesn’t affect fluctuation
D. They will have the same fluctuation, but the Css, av will be different

10. Superposition Describe the principle of superposition:
A. The drug concentration can be found by multiplying the initial concentration by the time elapsed.
B. The drug concentration is additive result of the concentration resulting from each individual dose administered.
C. The drug concentration is found by subtracting the concentration resulting from each individual dose administered.
D. The drug concentration is a divisible result of the concentration resulting from each individual dose administered.

11. Multiple IV Bolus Calculations

12. At Steady State, what happens to these equations?
Multiple IV dose
First arrow: This is the MDF
Second arrow: Add this portion if looking for C min or anything other than the Cmax (Remember if looking within the dosing interval, then must figure out how many hours into the dosing interval you are at)
Steady State: The top portion (1-e-nkTau) goes to 1
At Steady State, what happens to these equations?

13. Multiple IV Dose
HB is a 35 yo WM who is receiving 500mg of Levaquin every 12 hours for a UTI. Calculate the concentrations for the following times. The population values for CL and V are 4L/hr and 15L, respectively.
Time=0
Time=12 hours
0=33.3 mg/L
12=1.35 mg/L
24=34.6 mg/L
30=6.98 mg/L
48=34.67 mg/L
60=1.41 mg/L

14. Multiple IV Dose Time=24 hours Time= 30 hours Time= 48 hours

15. Multiple dosing oral
The population average values for the CL and Vd of nifedipine have been reported as 0.41 L/h/kg and 1.2 L/kg. What would be the maximum dosing interval you can use for a multiple-dose regimen with an immediate-release oral dosage form of nifedipine if peak-to-trough fluctuation should not exceed 100%?
A. 2 hours
B. 4 hours
C. 6 hours
D. 8 hours A

16. Multiple Dosing Oral Calculations

17. Multiple Dosing Oral
BR (58kg) will be started on an oral multiple-dose regimen with a new drug. The population values are CL=0.5 L/h/kg and V=6L/kg. The bioavailability is 0.9. Design an appropriate and reasonable oral dosing regimen that keeps the plasma concentrations at an average concentration of 1mg/L, with a peak-to-trough fluctuation less than or equal to 100%. (Oral dosage available as 150, 200, 250mg).
A. 150mg Q6H
B. 200mg Q4H
C. 200mg Q8H
D. 250mg Q8H D

18. Multiple dose short term infusion
500mg of Vancomycin is given as a short-term infusion over 1 hour every 8 hours
Blood samples were taken one hour after the end of the first infusion (C= 9.0 mg/L) and 30 min before the second dose was given (C=5.7 mg/L)
Optimize dose to achieve peak of 30mg/L and trough of 10mg/L
Find k
Find Cmax and Cmin
Find Vd
Find the dosing interval
Find D

19. Multiple Dosing Oral #4 on recitation—what did you get for the answer?
Oral multiple dose regimen with theophylline.
250mg in an immediate release dosage form (F=1), given Q6H
Three hours after (6.7mg/L), Six hours after (4.8mg/L)
Vd=30L
What trough concentration do you expect at Css?

20. Multiple Dose Short-Term Infusion Calculations

21. Multiple Dose Short Term Infusion
500mg of a new drug is given as a short-term infusion over 1 hour every 8 hours
Blood samples were taken one hour after the end of the first infusion (C= 9.0 mg/L) and 30 min before the second dose was given (C=5.7 mg/L). Optimize dose to achieve peak of 30mg/L and trough of 10mg/L
Find k
Find Cmax and Cmin

22. Find Vd
Find the dosing interval
Find D

23. Multiple Dose Short Term Infusion
Study tips:
Go through his step-by-step examples!
When you calculate k, what concentrations do you use?
When you calculate Vd, what concentrations do you use?

24. Questions?