BASIC PHARMACOKINETICS - CHAPTER 14: Exams I

CHAPTER 15 Practice Exams: Exam 2
Basic Pharmacokinetics REV. 99.4.25 15-1

Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
Practice Exams: Exam 2
15.1 Nifedipine: Exam 2

Nifedipine (Procardia @) is a calcium channel blocker which specifically inhibits potential-dependent channels not
receptor-operated channels, preventing calcium influx of cardiac and vascular smooth muscle (coronary, cerebral).
Calcium channel blockers reduce myocardial contractility and A-V node conduction by reducing the slow inward cal-
cium current. They are indicated in angina, cardiac dysrhythmias, and hypertension among others. Nifedipine
appears to be metabolized entirely into an inactive metabolite, an acid and subsequently further metabolized to a lac-
tone. Both the acid and the lactone are excreted into the urine and the feces.
Hepatic blood flow in normals is 1.6 L/min

Renal blood flow in normals is 1.2 L/min
Echizen and Eichelbaum (Clin Pkin 1986; 11:425-49) and Kleinbloesem et al (Clin Pcol Therap 1986; 40: 21-8)
reviewed the pharmacokinetics of Nifedipine. While the drug is not routinely given by IV bolus and does not strictly
conform to a one compartment model, let's treat the data as if those problems can be ignored. The following data is
offered for evaluation:
TABLE 1-1. Nifedipine IV Bolus Profile
Time (hr) Cp (mcg/L) Cm1 (mcg/L) Xm1f (mg) Xm1u (mg) Xm2f (mg) Xm2u (mg)
0.5 24.7
1 44.4
2 139 71.8 .14 .59
4 65.6 96.5 .44 1.83 .028 .11
6 31.1 100 .77 3.25 .073 .29
8 14.6 94.7 1.1 4.65 .135 .54
12 76.5 1.69 7.10 .291 1.15
24 34 2.77 11.63 .75 2.95
7 days 3.6 15.1 1.3 5.0
TABLE 1-2 Nifedipine Oral information
Brand Generic
Route IV Oral Capsule Oral Capsule
Dose (mg) 25 10 10
AUC (ug/L*hr) 785 236 204
AUMC (ug/L*hr2 ) 2093 866 816

Practice Exams: Exam 2 : Nifedipine: Exam 2
15.1.1 NIFEDIPINE QUESTIONS:

Find: 21) MRT (oral generic capsule) (hr)
1) MRT iv (hr) 22) MAT (oral generic capsule) (hr)
2) Ke (elimination rate constant) for Nife- 23) Ka, the apparent absorbtion rate con-
dipine (hr-1 ) stant, for the generic capsule (hr-1 )
3) T 1/2 for Nifedipine 24) Peak time for the generic capsule (hr)
4) Cp0 for iv dose (ug/L) 25) Cpmax , the maximum concentration
of the generic oral capsule give as a single
5) Vd for Nifedipine (L) dose (ug/L)
7) Cp of Nifedipine at one hour after the 26) Comparative bioavailability of the oral
IV dose capsules
8) AUC from 0 to one hour for the IV dose Your patient is controlled by 20 mg TID
9) Total Body Clearance of Nifedipine (L/ of the brand name oral capsule when he
hr) is healthy.
10) Renal Clearance of Nifedipine (L/hr) 27) What is his N for that dosing regimen?
11) Hepatic Clearance of Nifedipine (L/hr) 28) Cpssmax for this patient at this dosing
regimen (ug/L)
12) Renal Extraction Ratio
29) Cpssavg for this patient at this dosing
13) Hepatic Extraction Ratio
regimen (ug/L)
14) Absolute bioavailability for the brand
30) Cpssmin for this patient at this dosing
name capsule
regimen (ug/L)
15) MRT (oral brand name capsule) (hr)
You want to maintain his plasma con-
16) MAT (oral brand name capsule) (hr) centrations between 110% of Cpssmax
and 90% of Cpssmin . How would you
17) Ka, the apparent absorbtion rate con-
change the dosage regimen to if your
stant, for the brand name capsule (hr-1 )
patient suffered from:
18) Peak time for the brand name capsule
31) stenosis of the kidney (Fr = 0.67).
(hr)
32) renal failure (Fi = 0.67).
19) Cpmax , the maximum concentration
of the brand name oral capsule give as a 33) stenosis of the liver (Fr = 0.67)
single dose (ug/L)
34) cirrhosis of the liver (Fi = 0.67)
20) Absolute bioavailability for the generic
capsule

Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
TABLE 1-3 Nifedipine Answer Pool

Small Medium Large Dosing changes:
a) 0.00 a) 1.85 a) 59 a) 10 mg once daily
b) 0.05 b) 2.67 b) 85 b) 10 mg BID
c) 0.33 c) 3.67 c) 92.5 c) 10 mg TID
d) 0.375 d) 4.0 d) 101 d) 10 mg QID
e) 0.65 e) 4.32 e) 124 e) 20 mg once daily
f) 0.75 f) 9.3 f) 147 f) 20 mg BID
g) 0.85 g) 18.5 g) 185 g) 20 mg TID (no change necessary)
h) 1.0 h) 32 h) 202 h) 20 mg QID
i) 1.33 i) 38 i) 248 i) 30 mg once daily
j) 1.57 j) 49 j) 294 j) 30 mg BID

15.1.2 NIFEDIPINE SOLUTIONS

MRT iv = 2.67hr 21. Oral generic capsule
1.
MRT = 4hr
–1
2. k e = 0.375hr 22. Oral generic capsule
MAT = 1.33hr
3. T1 ⁄ 2 = 1.85hr
23. Oral generic capsule
4. Cp 0 = 294ug ⁄ L –1
Ka = 0.75hr
5. Vd = 85L 24. Oral generic capsule peak time
6. skip (error in numbering) 1.85hr
7. Cp 1 = 202ug ⁄ L 25. Oral generic capsule

Cp max = 38ug ⁄ L
8. AUC 0 – 1 = 248ug ⁄ L ⋅ hr
26. Comparative bioavailability of the
9. Cl s = 32L ⁄ hr oral capsules B/A:
AUC = 0.86 (ok)
10. Cl r = 0
Peak time = 1.18 (ok)
11. Cl h = 32L ⁄ hr Cpmax = 0.78 (not ok!)
12. Er = 0 27. N = 4.32

ss
13. Eh = 0.33 28. Cp max = 185ug ⁄ L
ss
14. Absolute bioavailability for brand 29. Cp ave = 59ug ⁄ L
name capsule = 0.75
ss
15. Oral brand name capsule 30. Cp min = 9.3ug ⁄ L
MRT = 3.67hr 31. No change
16. Oral brand name capsule 32. No change
MAT = 1.0hr 33. No change
17. Oral brand name capsule 34. No change
–1
Ka = 1.0hr
18. Oral brand name peak time
1.57hr
19. Oral brand name
Cp max = 49ug ⁄ L
20. Absolute bioavailability for
generic = 0.65

Practice Exams: Exam 2 : Valproate: Exam 2
15.2 Valproate: Exam 2

All questions are internally consistent. Information gained in any one can be used in all others. Note, however, there
is a change in patient status midway through.
Valproate is a carboxylic acid anticonvulsant. Its activity may be related, at least in part, to increase concentra-
tions of the neurotransmitter inhibitor gamma aminobutyric acid in the brain. It is used alone or in combination
with other anticonvulsants. in the prophylactic management of petit mal. It appears to be almost entirely cleared
by liver function with negligible amounts excreted into the urine unchanged. It comes as soft gelatin capsules of 250
mg and enteric coated tablets 250 and 500 mg. The therapeutic range for valproate appears to be between 20 and 100
mic/ml. The volume of distribution is 0.19 L/Kg and your patient is 70 kg.
TABLE 1-4
IV bolus Brand Generic

Dose (mg) 500 250 250
AUC (mg/L*hr) 594 273 253
AUMC(mg/L*hr ) 2 9428.6 4605.5 4184.6
Tpeak (hr) 2.95
Cpmax 14.35
Bioavailability (f) 1.0 .92

15.2.1 VALPROATE QUESTIONS

1) Calculate the MRTiv of Valproate (hr).
a) 11 b) 15.87 c) 16.54 d) 16.87 e) 17.08
2) Calculate the rate constant of elimination (hr-1 ) in normals ?

a) 0.091 b) 0.063 c) 0.060 d) 0.0593 e) 0.0585
3) Calculate the half life of Valproate (hr)?

a) 7.6 b) 11 c) 11.5 d) 11.7 e) 11.8
4) Calculate the hepatic clearance of valproate (L/hr).

a) 0.0084 b) 0.063 c) 0.84 d) 1.25 d) 2.5
5) Calculate the hepatic extraction ratio of valproate.

a) 0.0063 b) 0.0084 c) 0.063 d) 0.084 e) 0.84
6) What is the maximum N for multiple dosing of Valproate?

a) 0.78 b) 1.65 c) 2.12 d) 2.32 e) 2.5
7) What is the maximum acceptable dosing interval for normal patients (hr)?
a) 8 b) 12 c) 18 d) 24 e) 25.5
8) What is the N if we are going to dose TID?

a) 0.63 b) 0.727 c) 0.842 d) 1.25 e) 1.42
9) If you dosed this patient 500 mg BID with the brand name product, what would be your maximum concentration at
steady state (mg/L)?
a) 87.3 b) 70.9 c) 65.2 d) 52.8 e) 45.8
10) What would be your minimum concentration at steady state (mg/L)?

a) 52.8 b) 32.7 c) 30.1 d) 27.1 e) 22.9

11) What would be your average concentration at steady state (mg/L)?

a) 63.8 b) 49.8 c) 47.7 d) 45.8 e) 34.4
12) What loading dose would you give to get to Cpss right away (mg)?
a) 250 b) 500 c) 750 d) 1000 e) 1500
13) If you changed the dosage regimen to 250 mg QID, what would happen to the Cpssmax, Cpssave, Cpssmin?
a) Cpssmax - up, Cpssave - up, Cpssmin - up
b) Cpssmax - down, Cpssave - down, Cpssmin - down
c) Cpssmax - same, Cpssave - same, Cpssmin - same
d) Cpssmax - up, Cpssave - same, Cpssmin - down
e) Cpssmax - down, Cpssave - same, Cpssmin - up
14) Calculate f, the absolute bioavailability of the generic product.

a) 0.67 b) 0.75 c) 0.85 d) 0.93e) 1.0
15) Calculate the comparative bioavailability of the generic product.
a) 0.67 b) 0.75 c) 0.85 d) 0.93e) 1.0
16) Calculate the MRToral of the generic product.
a) 11 b) 15.87 c) 16.54 d) 16.87 e) 17.08
17) Calculate the MAT of the generic product.

a) 0.67 b) 0.75 c) 0.85 d) 0.93e) 1.0
18) Calculate the Ka of the generic product.

a) 1.5 b) 1.33 c) 1.18 d) 1.08 e) 1.0
19) Calculate the peak time of the generic product.

a) 2.21 b) 2.45 c) 2.59 d) 2.76 e) 2.95
20) Calculate the Cpmax of the generic product.

a) 8.1 b) 9.3 c) 10.7 d) 12.6 e) 14.4
21) Is the generic product bioequivalent?

a) Yes
b) No, because the comparative bioavailability is outside the federal guidelines.
c) No, because the ratio of the peak times is outside the federal guidlines.
d) No, because the ratio of the Cpmax s is outside the federal guidlines.
e) No, because the generic fails more than one of the required comparisons.
In patients who are also currently on phenobarbital their intrinsic clearance of valproate increases by 50% as the phe-
nobarbital induces the enzymes which metabolize valproate. Further questions refer to this condition.
22) Calculate his new clearance.

a) 0.0084 b) 0.063 c) 0.84 d) 1.25 d) 2.5
23) Calculate his new K.

a) 0.095 b) 0.084 c) 0.063 d) 0.059 e) 0.042
24) Calculate his new maximum acceptable dosing interval (hr).

a) 8 b) 12 c) 17 d) 18 e) 24
25) What dosage regimen would you recommend to try to maintain his plasma concentrations within 110% of the max-
imum and 90% of the minimum concentrations attained when he was normal?
a) 750 mg BID b) 500 mg TID c) 750 mg TID d) 250 mg QID e) 500 mg QID

15.2.2 VALPROATE SOLUTIONS

Practice Exams: Exam 2 : Methyl phenidate
15.3 Methyl phenidate

Methyl phenidate (MP) (Ritalin@) is an effective stimulant in the treatment of narcolepsy in adults and attention deficit
syndrome in children. It is entirely metabolized to the inactive metabolite, Ritalinic Acid (RA), by the liver which is
subsequently excreted unchanged into the urine. The following information was obtained from a 70 Kg male.
QH = 24 mL/min/Kg
QR = 19 mL/min/Kg
TABLE 1-5 Ritalin Data
Brand
IV Name Generic
Dose (mg) 10 20 20
AUC (ug/ml*hr) 0.20 0.04 0.035
AUMC (ug/ml*hr2 0.32 0.14 0.1225
TABLE 1-6 Ritalin Answer Pool
Itty- Bitty Tiny Puny Small Medium Large Words
a 0 0.016 0.1 1.1 10 100 yes

b 0.00016 0.0251 0.125 1.6 20 125 no, Ratio of Tps
c 0.0005 0.035 0.25 1.75 30 225 no, Ratio of Cmaxs
d 0.00074 0.042 0.35 1.9 40 375 no, Ratio of AUCs
e 0.00084 0.05 0.42 2.6 50 435 no, Ratio of AUMCs
f 0.0016 0.067 0.53 3.5 60 550 no, more than one criterion
g 0.005 0.075 0.625 4.2 70 675 20 mg TID
h 0.0074 0.0875 0.727 5.0 80 750 20 mg BID
i 0.0084 0.091 0.875 7.27 90 875 20 mg QD
j 0.0090 0.096 0.91 8.75 96 995 20 mg QID

15.3.1 METHYL PHENIDATE QUESTIONS:

1) MRT iv (hr) 25) Cpmax , the maximum concentration of
the generic oral tablet give as a single dose
2) Ke (elimination rate constant) for
(ug/mL)
Ritalin (hr-1 )
26) Comparative bioavailability of the oral
3) T 1/2 for Ritalin (hr)
tablets
4) Cp0 for iv dose (ug/mL)
27) Are the tablets bioequivalent?
5) Vd for Ritalin (L)
Your patient is controlled by 20 mg TID of
6) Cp of Ritalin at one hour after the IV the brand name oral tablet when he is
dose healthy. For This patient and this dosage
regimen, what is his:
7) AUC from 0 to one hour for the IV dose
28) N ?
8) Total Body Clearance of Ritalin (L/hr)
9) Renal Clearance of Ritalin (L/hr) 29) Cpssmax (ug/mL)
10) Hepatic Clearance of Ritalin (L/hr) 30) Cpssavg (ug/mL)
11) Intrinsic Hepatic Clearance of Ritalin 31) Cpssmin (ug/mL)

(L/hr) You want to maintain his plasma concen-
12) Renal Extraction Ratio trations between 110% of Cpssmax and 90% of
Cpssmin . How would you change the dosage
13) Hepatic Extraction Ratio regimen to if your patient suffered from:
14) Absolute bioavailability for the brand (in no case was there a change in Vd)
name tablet
32) stenosis of the kidney (Fr = 0.67)?
15) MRT (oral brand name tablet) (hr)
33) renal failure (Fi = 0.34)?
16) MAT (oral brand name tablet) (hr)
34) stenosis of the liver (Fr = 0.67)?
stant, for the brand name tablet (hr-1 ) 35) cirrhosis of the liver. (Fi = 0.67)?
18) Peak time for the brand name tablet 36) treatment with phenobarbital (Fi =
(hr) 1.33)?
19) Cpmax , the maximum concentration of
the brand name oral tablet give as a single
dose (ug/mL)
tablet
21) MRT (oral generic tablet) (hr)
22) MAT (oral generic tablet) (hr)
stant, for the generic tablet (hr-1 )
24) Peak time for the generic tablet (hr)

15.3.2 METHYL PHENIDATE SOLUTIONS:

1. MRT iv = 1.6hr 19. Brand name -
Cp max = 0.0084ug ⁄ mL
–1
2. k = 0.625hr
20. Generic - f = 0.0875
3. T1 ⁄ 2 = 1.1hr
21. Generic - MRT = 3.5hr
4. Cp 0 = 0.125ug ⁄ mL 22. Generic - MAT = 1.9hr
5. Vd = 80L –1
23. Generic - Ka = 0.53hr
6. Cp 1 = 0.067ug ⁄ mL
24. Generic - T peak = 1.75hr
7.
25. Generic -
AUC 0 – 1 = 0.096ug ⁄ mL ⋅ hr
Cp max = 0.0074ug ⁄ mL
8. Cl s = 50L ⁄ hr 26. Comparative bioavailability =
0.875
9. Cl r = 0
27. Yes, the tablets are bioequivalent -
10. Cl h = 50L ⁄ hr all parameters are within federal guide-
lines.
11. Cl int = 100L ⁄ hr
28. N = 7.27
12. Er = 0 ss
29. Cp max = 0.0251ug ⁄ mL
13. Eh = 0.53 ss
30. Cp avg = 0.005ug ⁄ mL
14. Brand name - f = 0.1
ss
31. Cp min = 0.00016ug ⁄ mL
15. Brand name - MRT = 3.5hr
32. 20 mg TID
16. Brand name - MAT = 1.9hr
33. 20 mg TID
–1 34. 20 mg BID
17. Brand name - Ka = 0.526hr
35. 20 mg TID
18. Brand name - Tpeak = 1.74hr
36. 20 mg QID


Practice Exams: Exam 2 : Verapamil
15.4 Verapamil
Verapamil is a calcium channel blocker with vasodilatory and antiarrhythmic effects. It is about 95% metabolized by
the liver with the metabolites showing up in the urine and feces.
Hepatic blood flow in normals is 1.6 L/min
Renal blood flow in normals is 1.2 L/min
TABLE 1-7 Verapamil Data
Brand Generic
Route IV Oral Tablet Oral Tablet

Dose (mg) 15 80 80
AUC (ng/mL*hr) 300 480 400
AUMC (ng/mL*hr2 ) 1600 2690 2280
TABLE 1-8 Verapamil Answer Pool
Tiny Small Medium Large Dosing regimens Bioavailability answers
a 0 1.06 26 116 40 mg qd Yes

b 0.063 2.15 46 267 40 mf bid No, tp ratio is not within limits
c 0.188 2.50 47.5 369 40 mg tid No, Cpmax ratio is not within limits
d 0.250 2.70 50 533 40 mg qid No, AUC ratio is not within limits
e 0.270 3.69 56 637 80 mg qd No, f ratio is not within limits
f 0.300 5.33 61.5 830 80 mg bid No, ka ratio is not within limits
g 0.370 5.60 76.5 905 80 mg tid No, ke ratio is not within limits
h 0.693 5.70 83 970 80 mg qid No, MRT ratio is not within limits
i 0.85 6.37 90.5 1160 160 mg qd No, Cl ratio is not within limits
j 0.905 8.30 97 2670 160 mg bid No, more than one of the required ratios are no within limits

15.4.1 VERAPAMIL QUESTIONS

1) MRT iv (hr) 23) Ka, the apparent absorbtion rate con-
stant, for the generic tablet (hr-1 )
2) Ke (elimination rate constant) for Vera-
pamil (hr-1 ) 24) Peak time for the generic tablet (hr)
3) T 1/2 for Verapamil 25) Cpmax , the maximum concentration
of the generic oral tablet give as a single
4) Cp0 for iv dose (ug/L)
dose (ug/L)
5) Vd for Verapamil (L)
26) Comparative bioavailability of the oral
7) Cp of Verapamil at one hour after the IV tablets
dose
Your patient is controlled by 80 mg TID
9) Total Body Clearance of Verapamil (L/ of the brand name oral tablet when he is
hr) healthy.
10) Renal Clearance of Verapamil (L/hr) 28) What is his N for that dosing regimen?
11) Hepatic Clearance of Verapamil (L/hr) 29) Cpssmax for this patient at this dosing
12) Renal Extraction Ratio regimen (ug/L)
13) Hepatic Extraction Ratio 30) Cpssavg for this patient at this dosing
regimen (ug/L)
14) Absolute bioavailability for the brand
name tablet 31) Cpssmin for this patient at this dosing
regimen (ug/L)
You want to maintain his plasma con-
16) MAT (oral brand name tablet) (hr) centrations between 110% of Cpssmax
17) Ka, the apparent absorbtion rate con- and 90% of Cpssmin . How would you
stant, for the brand name tablet (hr-1 ) change the dosage regimen to if your
patient suffered from:
18) Peak time for the brand name tablet
(hr) 32) stenosis of the kidney (Fr = 0.67). (No
change in volume of distribution.)
19) Cpmax , the maximum concentration
of the brand name oral tablet give as a sin- 33) renal failure (Fi = 0.34).(Volume of
gle dose (ug/L) distribution is reduced in this disease to
50% of normal)
tablet 34) stenosis of the liver (Fr = 0.67) (No
change in volume of distribution)
35) cirrhosis of the liver (Volume of Dis-
22) MAT (oral generic tablet) (hr) tribution and the bioavailability are both
doubled while the half life is quadrupled )

15.4.2 VERAPAMIL SOLUTIONS

1. MRT iv = 5.33hr 17. Brand name tablet -
–1
Ka = 3.69hr
–1
2. k e = 0.188hr
18. Brand name tablet - peak time -
3. T1 ⁄ 2 = 3.69hr 0.85hr
19. Brand name tablet -
4. Cp 0 = 56ug ⁄ L
Cp max = 76.5ug ⁄ L
5. Vd = 267L 20. Generic - Absolute bioavailability
6. skip - error in numbering - f = 0.25
7. Cp 1 = 47ug ⁄ L 21. Generic - MRT = 5.7hr
8. AUC 0 – 1 = 50ug ⁄ L ⋅ hr 22. Generic - MAT = 0.37hr

–1
9. Cl = 50L ⁄ hr 23. Generic - Ka = 2.70hr
10. Cl r = 2.50L ⁄ hr 24. Generic - T peak = 1.06hr
11. Cl h = 47.5L ⁄ hr 25. Generic - Cp max = 61.5ug ⁄ L
12. Er = 0.063 26. Comparative bioavailability - 0.85

27. The tablets are not bioequivalent -
13. Eh = 0.49 Correction - should peak time ratio is not within limits.
be added to answer pool
28. N = 2.15
14. Brand name tablet - absolute bio-
ss
availability = 0.30 29. Cp max = 116ug ⁄ L
ss
MRT = 5.60hr 30. Cp avg = 60ug ⁄ L (change in
answer pool)
ss
MAT = 0.270hr 31. Cp min = 26ug ⁄ L
32. No change in dosing regimen - 80
mg TID

33. 40 mg TID 35. 40 mg BID

34. No change in dosing regimen - 80
mg TID

Practice Exams: Exam 2 : Hydromorphone hydrochloride
15.5 Hydromorphone hydrochloride

Hydromorphone hydrochloride is an analog of morphine which has about seven times the analgesic effect of morphine
when given by IV. It is about 90% metabolized. The following data was obtained by Valner et al J.Clin Pcol 21(1981)
152-6:
TABLE 1-9 Hydromorphone hydrochloride Data
Oral tablet Oral tablet

IV Brand Generic
Dose (mg) 2 4 4
AUC (ng/mL*hr) 83 87 65
AUMC (ng/mL*hr2 ) 291 348 292

15.5.1 HYDROMORPHONE HYDROCHLORIDE QUESTIONS

For the IV product, find:
1. MRTiv. (291/83=3.5) 27. R(Bio)= 0.75 fail
2. K. (1/3.5=0.285 You would like to dose your healthy
3. T1/2 (0.693/.285= 2.4 hr) patient using the brand name tablet so
that his plasma concentration is in the
4. Cp0 (AUC*K = 83*0.285= 23.7ng/mL
therapeutic range of 35 to 5 ng/mL.
5. Ku (0.1*0.285=0.029) Find:
6. Km (0.9*0.285=0.256)
28. Nmax (ln(35/5)/ln(2) = 2.8
7. Cls (f*D/AUC=1*2000/83=24L/hr)
29. Taumax (2.8*2.4=6.74 hr
8. Vd (Cls/K=Vd= 24/0.285=84L
30. Maximum acceptable tau = 6
9. Clh (0.9*Cls = 21.6 L/hr
31. N (6/2.4 =2.5)
10. Clr (0.1*Cls = 2.4 L/hr
32. What dosage regimen would you recom-
11. Eh (21.6 / (24 mL/min * 60 min * 70 Kg /
mend? (4mg q6h)
1000mL/L) = 0.2
33. Cpssmax? (30 ng/mL)
12. Er ( 2.4 / ( 10 ml/min * 60 min * 70 Kg /
1000mL/L) = 0.06 34. Cpssavg? (14 ng/mL)
35. Cpssmin? ( 5 ng/mL)
For the Brand name oral tablet, find:

He gets renal stenosis (Fr = 0.5) with no
13. MRT (348/87=4.0)
change in Vd. Find:
14. MAT(4 - 3.5 = 0.5)
36. FClr0.94
15. Ka (1/0.5 = 2.0)
37. Clr*2.3
16. Tp (ln(ka/K)/(ka-K)=1.95/1.715=1.14hr
38. FClh1
17. Absolute bioavailability, f ((87/4)/(83/
2)=0.52 39. Clh*21.6
18. Cpmax (18 ng/mL) 40. FCls.99
41. Cls*23.9
For the Generic oral tablet, find: 42. K*0.284
43. t1/2*2.44
19. MRT ( 292/65=4.5 hr)
44. Nmax 2.8
20. MAT (4.5 - 3.5 = 1 hr)
45. Taumax6.83
21. ka (1/MAT = 1/1=1 hr-1)
46. Maximum acceptable tau 6
22. Tp (ln(1/0.285)/(1-0.285)=1.26/.715=1.76
47. N 2.46
hr
23. Absolute bioavailability, f ((65/4)/(83/ 48. What dosage regimen would you recom-
2)=0.39 mend? 4mg q6h
49. Cpssmax? 30
24. Cpmax (11 ng/mL)
50. Cpssavg? 15
51. Cpssmin? 5.5
Would you consider the oral tablets to
be bioequivalent? Why or why not?
His stenosis of the kidney clears and he
25. No R(Tp) = 1.54 fail
now goes into renal dysfunction
26. R(Cp) = 0.61 fail (Fi=0.5), find:

52. FClr.52 77. Taumax8

53. Clr*1.23 78. Maximum acceptable tau 8
54. FClh2 79. N6
55. Clh*21.6 80. What dosage regimen would you recom-
56. FCls.95 mend? 4 mg q6h
57. Cls*22.8 81. Cpssmax? 32
58. K*0.271 82. Cpssavg? 17
59. t1/2*2.55 83. Cpssmin? 7.5
60. Nmax 2.8
61. Taumax 7.13 His stenosis of the liver clears and he
62. Maximum acceptable tau6 now suffers from liver dysfunction
63. N 2.35
(Fi=0.05), Find:
64. What dosage regimen would you recom- 84. FClr1
mend? 4mg q6h 85. Clr*2.4
65. Cpssmax? 31 86. FClh.56
66. Cpssavg? 15 87. Clh*12
67. Cpssmin? 6.1 88. FCls.6
89. Cls*14.4
His renal dysfunction clears and now he 90. K*.171
suffers from stenosis of the liver 91. t1/2*4.04
(Fr=0.5), Find: 92. Nmax 2.8
68. FClr1 93. Taumax11.3
69. Clr*2.4 94. Maximum acceptable tau8
70. FClh.833 95. N 1.48
71. Clh*18 96. What dosage regimen would you recom-
72. FCls.85 mend?4 mg q8h
73. Cls*20.4 97. Cpssmax? 33
74. K*.243 98. Cpssavg? 18
75. t1/2*2.85 99. Cpssmin?8.4
76. Nmax 2.8


15.6 Fosinopril Sodium

Fosinopril Sodium (MW 585) is a phosphinic prodrug of the angiotensin converting enzyme (ACE) inhibitor fosinopri-
lat (MW 563). After oral administration, fosinopril is slowly and incompletely absorbed, and is converted to the active
fosinoprolat by esterases in the gastrointestinal mucosa and the liver. Unlike other ACE inhibitors, elimination of fosi-
noprilat is divided equally between renal and hepatic pathways. With the IV dose fosinoprilat was given and mea-
sured. With the oral dose fosinopril was given but fosinoprilat was measured. The following information was obtained
from a 70 Kg male. This information was constructed from Kostis et al “Fosinopril: Pharmacokinetics and pharmaco-
dynamics in congestive heart failure” Clin Pcol Ther 58(6) 660-5 (1995); Hui et al “Pharmacokinetics of fosinopril in
patients with various degrees of renal function” Clin Pcol Ther 49(4) 457 -66 (1991)
QH = 24 mL/min/Kg Blood
QR = 19 mL/min/Kg Blood
TABLE 1-10 Fosinopril Data
IV Brand Name Generic

Tablet Tablet
Dose (mg) 7.5 10 10
AUC (ng/ml*hr) 5700 1500 1400
AUMC (ng/ml*hr2) 78000 25000 23100
TABLE 1-11 Fosinopril Answer Pool:
a 0 0.015 0.19 1.3 10 100 yes

b 0.00016 0.0251 0.21 1.6 13.7 142 no, Ratio of Tps
c 0.0005 0.035 0.25 1.75 16.6 192 no, Ratio of Cmaxs
d 0.00074 0.042 0.36 1.9 18 253 no, Ratio of AUCs
e 0.00084 0.05 0.42 2.8 50 387 no, Ratio of AUMCs
f 0.0016 0.067 0.53 3.5 67 402 no, more than one criterion
g 0.005 0.073 0.65 4.0 73 416 10 mg qid
h 0.0064 0.0875 0.72 5.6 84 750 10 mg tid
i 0.0084 0.091 0.84 7.0 93 875 10 mg bid
j 0.0090 0.096 0.93 9.5 96 995 10 mg qd

15.6.1 FOSINOPRIL QUESTIONS

1) MRT for fosinoprilat (hr)
2) Ke for fosinoprilat (hr-1)
3) T ? for Fosinoprilat (hr)
4) Cp0 for iv dose (ng/mL)
5) Vd for Fosinoprilat (L)

6) Cp of Fosinoprilat at one hour after the IV dose
8) Total Body Clearance of Fosinoprilat (L/hr)
9) Renal Clearance of Fosinoprilat (L/hr)
10) Hepatic Clearance of Fosinoprilat (L/hr)
11) Intrinsic Hepatic Clearance of Fosinoprilat (L/hr)
12) Renal Extraction Ratio
13) Hepatic Extraction Ratio
14) Absolute bioavailability for the brand name tablet
16) MAT (oral brand name tablet) (hr)
17) Ka, the apparent absorption rate constant, for the brand name tablet (hr-1 )
18) Peak time for the brand name tablet (hr)

19) Cpmax , the maximum concentration of the brand name oral tablet give as a single dose (ng/mL)
20) Absolute bioavailability for the generic tablet
22) MAT (oral generic tablet) (hr)
23) Ka, the apparent absorption rate constant, for the generic tablet (hr-1 )
24) Peak time for the generic tablet (hr)

25) Cpmax , the maximum concentration of the generic oral tablet give as a single dose (ng/mL)
26) Comparative bioavailability of the oral tablets
Your patient is controlled by 10 mg TID of the brand name oral tablet when he is
healthy. For This patient and this dosage regimen, what is his:
28) N ?

29) Cpssmax (ng/mL)

30) Cpssavg (ng/mL)
31) Cpssmin (ng/mL)
You want to maintain his plasma concentrations between 120% of Cpssmax and 80% of
Cpssmin . How would you change the dosage regimen to if your patient suffered from:
(in no case was there a change in Vd)

32) stenosis of the kidney (Fr = 0.67)?
33) renal failure (Fi = 0.34)?
34) stenosis of the liver (Fr = 0.67)?
35) cirrhosis of the liver. (Fi = 0.67)?
36) treatment with phenobarbital (Fi = 1.5)?

Practice Exams: Exam 2 : Fosinopril Sodium
15.6.2 FOSINOPRIL SODIUM SOLUTIONS

1. MRT = 13.7hr 19. Oral brand name tablet
Cp max = 0.073ng ⁄ mL
–1
2. k = 0.073hr
20. Oral generic tablet absolute bio-
3. T1 ⁄ 2 = 9.5hr availability is 0.19
21. Oral generic tablet
4. Cp 0 = 416ng ⁄ mL
MRT = 16.6hr
5. Vd = 18L 22. Oral generic tablet
6. Cp 1 = 387ng ⁄ mL MAT = 2.8hr
–1
7. AUC 0 – 1 = 402ng ⁄ mL 23. Generic tablet Ka = 0.36hr
24. Generic tablet peak time 5.6hr

8. Cl s = 1.3L ⁄ hr
25. Generic tablet
9. Cl r = 0.65L ⁄ hr Cp max = 0.067ng ⁄ mL
10. Cl h = 0.65L ⁄ hr 26. Comparative bioavailability of the
oral tablets = 0.93
11. Intrinsic Hepatic Clearance is
27. Yes! the tablets are bioequivalent
0.65L ⁄ hr
The AUCs, peak times, and Cp max s are
12. Er = 0.015 all within 20% range.
13. Eh = 0.0064 28. N = 0.84

ss
14. Oral brand name tablet absolute 29. Cp max = 253ng ⁄ mL
bioavailability is 0.21
ss
15. Oral brand name tablet 30. Cp avg = 192ng ⁄ mL
MRT = 16.6hr ss
31. Cp min = 142ng ⁄ mL
16. Oral brand name tablet
MAT = 2.8hr 32. 10 mg TID
17. Oral brand name tablet 33. 10 mg BID

–1 34. 10 mg TID
Ka = 0.36hr
35. 10 mg TID
18. Oral brand name tablet peak time
5.6hr 36. 10 mg QID


15.7 Remoxipride
Remoxipride (MW 296 - Unionized Base pKa 9.4) is a new antipsychotic of the benzamide type (See figure 1). The
pharmacokinetics were studied by Movin-Osswald and Hammarlind-Udenaes (Brit. J Clin Pcol 1991 32(3) 355ff).
Their results are summarized in table 1. The HCl salt of the drug was given (MW 332.5) to these patients in this study
but the drug concentration was reported as the free base in the plasma. In this study, 25% of the Remoxipride was
excreted unchanged, 75% was metabolized. The hepatic and renal blood flow in these patients was 1.5 and 1.2 L/min
respectively. REMEMBER TO PAY ATTENTION TO UNITS.
FIGURE 4-5. Remoxipride
TABLE 1-12 Remoxipride Data
IV bolus Oral Solution Tablet A Tablet B
Dose (mg) 50 100 100
AUMC (umole/ 145 158.7 319.6 282.6

L*hr2 )
AUC (umole/L*hr) 20.9 19.8 37.6 31.4
Tp (hr) 3.6
Cpmax (mg/L) .8
f .75

15.7.1 REMOXIPRIDE QUESTIONS

1) Find the MRT of the IV product (hr).
2) Find the elimination rate constant of remoxipride (hr-1 ).
3) Find the Cp0 of the IV product (mg/L)
4) Find the volume of distribution of the IV product. (L)
5) Find the half life of remoxipride (hr).
6) Find the clearance of remoxipride (L/hr).
7) Find the renal clearance (L/hr).
8) Find the hepatic clearance
9) Find the renal extraction ratio.
10) Find the hepatic extraction ratio.
11) Find the MRT of remoxipride given as the oral solution (hr).
12) Find the MAT of remoxipride given as oral solution (hr).
13) Find the absorption rate constant of remoxipride given as an oral solution (hr-1 ).
14) Find the bioavailability of the oral solution (f).
15) Find the peak time of the oral solution (hr).
16) Find the MRT of remoxipride given as Tablet A, the brand name product.
17) Find the MAT of remoxipride given as Tablet A.
18) Find the apparent absorption rate constant (ka) of remoxipride given as Tablet A.
19) Find the peak time of Tablet A.
20) Find the single dose Cpmax for tablet A (mg/L)
21) Find the mean dissolution time (MDT) of Tablet A, the brand name product (hr).
22) Is Tablet B, the generic product is bioequivalent to Tablet A. Why or why not?
23) Find N for BID dosing.
24) Find Cpss max for two caps bid for the brand name product.
25) Find Cpss avg for two caps bid for the brand name product.
26) Find Cpss min for two caps bid for the brand name product.
27) Which change in physiological status would result in the most significant change in
the TBC of remoxipride?
a) Changes which effect the flow of blood to the liver.
b) Changes which effect the flow of blood to the kidney.
c) Changes which effect the function of the liver.

d) Changes which effect the function of the kidney.

Your patient is experiencing that change. That physiological function was up 75% above
normal (F = 1.75).
28) Find his new renal clearance
29) Find his new hepatic clearance.
30) Find his new total body clearance.
31) Assuming now change in volume of distribution, find his new half life.
32 Assuming no change in dosage regimen, find his new N.
33 What dosing regimen would you recommend to return his plasma concentrations back
to normal (within 110% of max and 90% of min)?

15.7.2 REMOXIPRIDE SOLUTIONS

1. MRT = 6.93hr
–1
2. k e = 0.144hr
3. Cp 0 = 0.88mg ⁄ L
4. Vd = 50L
5. T1 ⁄ 2 = 4.8hr
6. Cl = 7.28L ⁄ hr
7. Cl r = 1.8L ⁄ hr
8. Cl h = 5.46L ⁄ hr
9. Er = 0.025
10. Eh = 0.06
11. Oral solution MRT = 8hr
12. Oral solution MAT = 1.07hr

–1
13. Oral solution Ka = 0.935hr
14. Oral solution bioavailability f = 0.95
15. Oral solution peak time 2.4hr
16. Tablet A MRT = 8.5hr
17. Tablet A MAT = 1.57hr

–1
18. Tablet A Ka = 0.637hr
19. Tablet A peak time 3.0hr
20. Tablet A single dose Cp max = 1.03mg ⁄ L
21. Tablet A MDT = 0.5hr
22. Tablet B is not bioequivalent to Tablet A because peak time and Cp max are out of
federal guidelines.
23. For dosing BID, N = 2.5

ss
24. Cp max = 3.88mg ⁄ L
ss
25. Cp avg = 1.85mg ⁄ L
ss
26. Cp min = 0.685mg ⁄ L
27. The change in physiological status that would result in the most significant change
in TBC of remoxipride is (C) - changes
which effect the function of the liver.
28. New renal clearance = no change
29. New Cl h = 9.0L ⁄ hr
30. New Cl s = 10.8L ⁄ hr
31. New T1 ⁄ 2 = 3.2hr
32. New N = 3.75

33. The dosing regimen to recommend = 200 mg TID

15.8 Naproxen
Naprosyn@ (naproxen) is a nonsteroidal anti-inflammatory drug (NSAID) with
analgesic properties. It is well absorbed (f = 0.95) and highly protein bound (98%)
with a volume of distribution of about 10 L and a half-life of 13 hours in normal
adults. It is almost entirely cleared by hepatic function (CLr = 1%) with about one-
third being metabolized to the 6-o-desmethylnaproxen (which is further metabo-
lized by conjugation) and two-thirds being conjugated directly. Both the 6-o-des-
methyl metabolites as well as the conjugates are inactive.
Normal dosing is 500 mg Naproxen BID. You stock 200 and 500 mg tablets in
your HMO.
For the following conditions, new parameters are given in parentheses.
Concomitant treatment with Probenecid, a uricosuric which increases the urinary

excretion of uric acid, while not interfering with the protein binding, effectively
blocks the hepatic conjugation process reducing the hepatic function (Clinth ) to
one-third of normal.
In chronic renal failure (Fir = 0.1) the protein binding is reduced (94%) because of
uremia. This results in a marginal increase in half-life (14 hr.)
In rheumatoid arthritis, hypoalbuminaemia results in a reduction in protein binding

(97%) and increase in the volume of distribution (13 L).
Elderly patients exhibit a decrease in binding (96%), but no change in half-life or

volume of distribution.
For each of the conditions, (with Probenecid, chronic renal failure, arthritic, and
elderly), please recommend a dosage regimen which would give approximately the
same plasma concentrations of free naproxen obtained in the normal case (+ 10%.)
Constants:
L - renal blood perfusion ⋅ 70kg ⋅ 60min
Q r = 0.0191 ------------------- L
--------- ≈ 80 -----blood
min ⋅ kg hr hr
L min L
Q H = 0.0238 -------------------- hepatic blood perfusion ⋅ 70kg ⋅ 60--------- ≈ 100 -----blood
min ⋅ kg hr hr
Extraction ratios are calculated for normals and considered to be constant through-
out.

15.8.1 NAPROXEN QUESTIONS

TABLE 1-1. Question Numbers For Exam
Patient Condition Normal Probenecid Chronic Rheumatoid Elderly
treatment Renal Failure arthritis
Dose(mg) 1 27 51 75 99
f 2 28 52 76 100
fu 3 29 53 77 101
Vd (L) 4 30 54 78 102
k (hr-1) 5 31 55 79 103
T 1/2 (hr) 6 32 56 80 104
AUC (mg/L*hr) 7 33 57 81 105
% Cl h 8 34 58 82 106
% Cl r 9 35 59 83 107
Cl tot (L/hr) 10 36 60 84 108
Cl h (L/hr) 11 37 61 85 109
Cl r (L/hr) 12 38 62 86 110
Eh 13
Er 14
Cl h (L/hr) 15 39 63 87 111
int
Cl r (L/hr) 16 40 64 88 112
int
FR h 17 41 65 89 113
FI h 18 42 66 90 114
FR r 19 43 67 91 115
FI r 20 44 68 92 116
FCL 21 45 69 93 117
τ (hr) 22 46 70 94 118
N 23 47 71 95 119
ss µg  24 48 72 96 120
Cp  -------
-
max free  mL

ss  µg  25 49 73 97 121
Cp --------
avg free  mL
ss µg  26 50 74 98 122
Cp  -------
-
min free  mL
Answer Pool
S M L XL XXL XXXL
A 0.000067 0.0182 0.100 1.0 10.0 100
B 0.0005 0.0200 0.133 1.1 11.3 200
C 0.0050 0.0300 0.177 1.4 12.0 303
D 0.0080 0.0400 0.182 1.5 13.0 356
E 0.0089 0.0495 0.267 1.6 13.3 500
F 0.0092 0.0533 0.315 1.7 14.0 595
G 0.0095 0.0600 0.333 1.8 26.5 891
H 0.0097 0.0610 0.341 1.9 31.7 1044
I 0.0098 0.0675 0.528 2.0 38.1 2000
J 0.0099 0.0700 0.533 2.1 45.0 3000
A 0.0790 0.577 2.2 50.0
B 0.0798 0.615 2.9 53.0
C 0.0857 0.675 3.0 62.0
D 0.0923 0.700 5.3 80.0
E 0.0950 0.790 6.2 86.0
F 0.0970 0.798 8.0 92.0
G 0.0990 0.857 8.5 97.0
I 0.0999 0.923 9.0 99.0
J 0.09997 0.95 9.9 99.97

15.8.2 NAPROXEN SOLUTIONS

TABLE 1-1. Question Numbers For Exam
Patient Condition Normal Probenecid Chronic Rheumatoid Elderly
treatment Renal Failure arthritis
Dose(mg) 1. 500 mg 27. 200 51. 500 75. 500 99. 200
f 2. 0.95 28. 0.95 52. 0.95 76. 0.95 100. 0.95
fu 3. 0.02 29. 0.02 53. 0.06 77. 0.03 101. 0.04
Vd (L) 4. 10 30. 10 54. 31.67 78. 13 102. 10
k (hr-1) 5. 0.0533 31. 0.0182 55. 0.0495 79. 0.061 103. 0.533
T 1/2 (hr) 6. 13 32. 38.1 56. 14 80. 11.3 104. 13
AUC (mg/L*hr) 7. 891 33. 1044 57. 303 81. 595 105. 356
% Cl h 8. 99 34. 97 58. 99.97 82. 99 106. 99
% Cl r 9. 1 35. 3 59. 0.03 83. 1 107. 1
Cl tot (L/hr) 10. 0.533 36. 0.182 60. 1.57 84. 0.798 108. 0.533
Cl h (L/hr) 11. 0.528 37. 0.177 61. 1.57 85. 0.790 109. 0.528
Cl r (L/hr) 12. 0.005 38. 0.005 62. 0.005 86. 0.008 110. 0.005
Eh 13. 0.005
Er 14. 0.000067
Cl h (L/hr) 15. 26.5 39. 8.84 63. 26.5 87. 26.5 111. 13.26
int
Cl r (L/hr) 16. 0.267 40. 0.267 64. 0.00889 88. 0.267 112. 0.133
int
FR h 17. 1 41. 1 65. 1 89. 1 113. 1
FI h 18. 1 42. 0.333 66. 3 90. 1.5 114. 1
FR r 19. 1 43. 1 67. 1 91. 1 115. 1
FI r 20. 1 44. 1 68. 0.1 92. 1.5 116. 1
FCL 21. 1 45. 0.341 69. 2.94 93. 1.5 117. 1
τ (hr) 22. 12 46. 12 70. 12 94. 12 118. 8

N 23. 0.923 47. 0.315 71. 0.857 95. 1.06 119. 0.615
ss µg- 24. 2.01 48. 1.94 72. 2.01 96. 2.1 120. 2.2
Cp  -------
max free  mL
ss µg- 25. 1.5 49. 1.74 73. 1.5 97. 1.5 121. 1.78
Cp  -------
avg free  mL
ss µg  26. 1.06 50. 1.55 74. 1.1 98. 1.01 122. 1.42
Cp  -------
-
min free  mL

15.8.3
1. Dose = 500 mg (given)
2. Bioavailability (f) = 0.95 (given)
3. Unbound Fraction = 0.02 (given)
4. V d = 10L (given)
0.693 –1
5. k = ------------- = 0.0533hr
t1 ⁄ 2
6. t 1 ⁄ 2 = 13hr (given)
f ⋅ Dose
7. AUC = ------------------- = 891L
k ⋅ Vd
8. %Cl h = 100 – %Cl r = 99
9. %Cl r = 1 (given)
10. Cl tot = k ⋅ V d = 0.533L ⁄ hr
11. Cl h = Cl tot ⋅ %Cl h = 0.528L ⁄ hr
12. Cl r = Cl tot ⋅ %Cl r = 0.005L ⁄ hr
Cl
13. E h = -------h- = 0.00528
Qh
Cl
14. E r = --------r = 0.000067
Qr
Q ⋅ Cl h
------------------
Q – Cl
15. Cl h = ------------------h- = 26.5L ⁄ hr
int
fu
Q ⋅ Cl
-----------------r-
Q – Cl
16. Cl r = ------------------r = 0.267L ⁄ hr
int
fu
17. FR h = 1 (given)
18. FI h = 1 (given)

19. FR r = 1 (given)
20. FI r = 1 (given)
21. F Cl = 1 (given)
22. τ = 12hr (given)
τ
23. N = --------- = 0.923
t1 ⁄ 2
ss fu ⋅ S ⋅ f ⋅ D 1 µg-
24. Cp = -------------------------- ⋅ -------------------- = 2.0 -------
N
1 –  ---
max free V 1 mL
2
ss f u ⋅ S ⋅ f ⋅ D fu ⋅ S ⋅ f ⋅ D µg-
25. Cp = -------------------------- = ------------------------------ = 1.5 -------
avg free V⋅K⋅τ V ⋅ 0.693 ⋅ N mL
N
 1---
ss fu ⋅ S ⋅ f ⋅ D  2 µg-
26. Cp = -------------------------- ⋅ -------------------- = 1.1 -------
N
1 –  1---
min free V mL
2
27. Dose = mg
28. Bioavailability (f) = 0.95 (no change)
29. Unbound Fraction = 0.02 (no change - given)
30. V d = 10L (given)
0.693
31. k = ------------- = 0.0533hr
–1
t1 ⁄ 2
32. t 1 ⁄ 2 = 13hr (given)
f ⋅ Dose
33. AUC = ------------------- = 891L
k ⋅ Vd
34. %Cl h = 100 – %Cl r = 99
35. %Cl r = 1 (given)
36. Cl tot = k ⋅ V d = 0.533L ⁄ hr
37. Cl h = Cl tot ⋅ %Cl h = 0.528L ⁄ hr

38. Cl r = Cl tot ⋅ %Cl r = 0.005L ⁄ hr
Q ⋅ Cl h
------------------
Q – Cl
39. Cl h = ------------------h- = 26.5L ⁄ hr
int
fu
Q ⋅ Cl
-----------------r-
Q – Cl
40. Cl r = ------------------r = 0.267L ⁄ hr
int
fu
τ
47. N = --------- = 0.923
t1 ⁄ 2
ss fu ⋅ S ⋅ f ⋅ D 1 µg-
48. Cp = -------------------------- ⋅ -------------------- = 2.0 -------
N
1 –  1---
max free V mL
2
ss f u ⋅ S ⋅ f ⋅ D fu ⋅ S ⋅ f ⋅ D µg-
49. Cp = -------------------------- = ------------------------------ = 1.5 -------
N
 1---
ss fu ⋅ S ⋅ f ⋅ D  2 µg-
50. Cp = -------------------------- ⋅ -------------------- = 1.1 -------
N
1 –  1---
min free V mL
2
51. Dose = mg
54. V d = 10L (given)

0.693 –1
55. k = ------------- = 0.0533hr
t1 ⁄ 2
56. t 1 ⁄ 2 = 13hr (given)
f ⋅ Dose
57. AUC = ------------------- = 891L
k ⋅ Vd
58. %Cl h = 100 – %Cl r = 99
59. %Cl r = 1 (given)
60. Cl tot = k ⋅ V d = 0.533L ⁄ hr
61. Cl h = Cl tot ⋅ %Cl h = 0.528L ⁄ hr
62. Cl r = Cl tot ⋅ %Cl r = 0.005L ⁄ hr
Q ⋅ Cl h
------------------
Q – Cl
63. Cl h = ------------------h- = 26.5L ⁄ hr
int fu
Q ⋅ Cl
-----------------r-
Q – Cl
64. Cl r = ------------------r = 0.267L ⁄ hr
int fu
τ
71. N = --------- = 0.923
t1 ⁄ 2
ss fu ⋅ S ⋅ f ⋅ D 1 µg-
72. Cp = -------------------------- ⋅ -------------------- = 2.0 -------
1 –  1---
max free V N mL
2

ss f u ⋅ S ⋅ f ⋅ D fu ⋅ S ⋅ f ⋅ D µg-
73. Cp = -------------------------- = ------------------------------ = 1.5 -------
 1--- N
ss fu ⋅ S ⋅ f ⋅ D  2 µg-
74. Cp = -------------------------- ⋅ -------------------- = 1.1 -------
1 –  1---
min free V N mL
2
75. Dose = mg
78. V d = 10L (given)
0.693 –1
79. k = ------------- = 0.0533hr
t1 ⁄ 2
80. t 1 ⁄ 2 = 13hr (given)
f ⋅ Dose
81. AUC = ------------------- = 891L
k ⋅ Vd
82. %Cl h = 100 – %Cl r = 99
83. %Cl r = 1 (given)
84. Cl tot = k ⋅ V d = 0.533L ⁄ hr
85. Cl h = Cl tot ⋅ %Cl h = 0.528L ⁄ hr
86. Cl r = Cl tot ⋅ %Cl r = 0.005L ⁄ hr
Q ⋅ Cl h
------------------
Q – Cl
87. Cl h = ------------------h- = 26.5L ⁄ hr
int fu
Q ⋅ Cl
-----------------r-
Q – Cl
88. Cl r = ------------------r = 0.267L ⁄ hr
int fu

τ
95. N = --------- = 0.923
t1 ⁄ 2
ss fu ⋅ S ⋅ f ⋅ D 1 µg-
96. Cp = -------------------------- ⋅ -------------------- = 2.0 -------
N
1 –  ---
max free V 1 mL
2
ss f u ⋅ S ⋅ f ⋅ D fu ⋅ S ⋅ f ⋅ D µg-
97. Cp = -------------------------- = ------------------------------ = 1.5 -------
N
 1---
ss fu ⋅ S ⋅ f ⋅ D  2 µg-
98. Cp = -------------------------- ⋅ -------------------- = 1.1 -------
N
1 –  1---
min free V mL
2
99. Dose = mg
102. V d = 10L (given)
0.693 –1
103. k = ------------- = 0.0533hr
t1 ⁄ 2
104. t1 ⁄ 2 = 13hr (given)
f ⋅ Dose
105. AUC = ------------------- = 891L
k ⋅ Vd
106. %Cl h = 100 – %Cl r = 99
107. %Cl r = 1 (given)
108. Cl tot = k ⋅ V d = 0.533L ⁄ hr
109. Cl h = Cl tot ⋅ %Cl h = 0.528L ⁄ hr

110. Cl r = Cl tot ⋅ %Cl r = 0.005L ⁄ hr
Q ⋅ Cl h
------------------
Q – Cl
111. Cl h = ------------------h- = 26.5L ⁄ hr
int
fu
Q ⋅ Cl
-----------------r-
Q – Cl
112. Cl r = ------------------r = 0.267L ⁄ hr
int
fu
113. FR h = 1 (given)
114. FI h = 1 (given)
115. FR r = 1 (given)
116. FI r = 1 (given)
117. F Cl = 1 (given)
118. τ = 12hr (given)
τ
119. N = --------- = 0.923
t1 ⁄ 2
ss fu ⋅ S ⋅ f ⋅ D 1 µg-
120. Cp = -------------------------- ⋅ -------------------- = 2.0 -------
N
1 –  1---
max free V mL
2
ss fu ⋅ S ⋅ f ⋅ D f u ⋅ S ⋅ f ⋅ D µg-
121. Cp = -------------------------- = ------------------------------ = 1.5 -------
N
 1---
ss fu ⋅ S ⋅ f ⋅ D  2 µg-
122. Cp = -------------------------- ⋅ -------------------- = 1.1 -------
N
1 –  1---
min free V mL
2


BASIC PHARMACOKINETICS - CHAPTER 14: Exams I

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BASIC PHARMACOKINETICS - CHAPTER 14: Exams I

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CHAPTER 15 Practice Exams: Exam 2

Basic Pharmacokinetics REV. 99.4.25 15-1

15.1 Nifedipine: Exam 2

Hepatic blood flow in normals is 1.6 L/min

TABLE 1-2 Nifedipine Oral information

Basic Pharmacokinetics REV. 99.4.25 15-2

15.1.1 NIFEDIPINE QUESTIONS:

Basic Pharmacokinetics REV. 99.4.25 15-3

TABLE 1-3 Nifedipine Answer Pool

Basic Pharmacokinetics REV. 99.4.25 15-4

15.1.2 NIFEDIPINE SOLUTIONS

7. Cp 1 = 202ug ⁄ L 25. Oral generic capsule

12. Er = 0 27. N = 4.32

Basic Pharmacokinetics REV. 99.4.25 15-5

15.2 Valproate: Exam 2

IV bolus Brand Generic

Tpeak (hr) 2.95

Bioavailability (f) 1.0 .92

Basic Pharmacokinetics REV. 99.4.25 15-6

15.2.1 VALPROATE QUESTIONS

a) 11 b) 15.87 c) 16.54 d) 16.87 e) 17.08

2) Calculate the rate constant of elimination (hr-1 ) in normals ?

3) Calculate the half life of Valproate (hr)?

4) Calculate the hepatic clearance of valproate (L/hr).

5) Calculate the hepatic extraction ratio of valproate.

6) What is the maximum N for multiple dosing of Valproate?

8) What is the N if we are going to dose TID?

10) What would be your minimum concentration at steady state (mg/L)?

Basic Pharmacokinetics REV. 99.4.25 15-7

11) What would be your average concentration at steady state (mg/L)?

14) Calculate f, the absolute bioavailability of the generic product.

16) Calculate the MRToral of the generic product.

a) 11 b) 15.87 c) 16.54 d) 16.87 e) 17.08

17) Calculate the MAT of the generic product.

18) Calculate the Ka of the generic product.

19) Calculate the peak time of the generic product.

20) Calculate the Cpmax of the generic product.

Basic Pharmacokinetics REV. 99.4.25 15-8

a) 8.1 b) 9.3 c) 10.7 d) 12.6 e) 14.4

21) Is the generic product bioequivalent?

22) Calculate his new clearance.

23) Calculate his new K.

24) Calculate his new maximum acceptable dosing interval (hr).

Basic Pharmacokinetics REV. 99.4.25 15-9

15.2.2 VALPROATE SOLUTIONS

Basic Pharmacokinetics REV. 99.4.25 15-10

15.3 Methyl phenidate

TABLE 1-5 Ritalin Data

TABLE 1-6 Ritalin Answer Pool

Itty- Bitty Tiny Puny Small Medium Large Words

a 0 0.016 0.1 1.1 10 100 yes

Basic Pharmacokinetics REV. 99.4.25 15-11

15.3.1 METHYL PHENIDATE QUESTIONS:

10) Hepatic Clearance of Ritalin (L/hr) 30) Cpssavg (ug/mL)

11) Intrinsic Hepatic Clearance of Ritalin 31) Cpssmin (ug/mL)

Basic Pharmacokinetics REV. 99.4.25 15-12

15.3.2 METHYL PHENIDATE SOLUTIONS:

Basic Pharmacokinetics REV. 99.4.25 15-13

Basic Pharmacokinetics REV. 99.4.25 15-14

Route IV Oral Tablet Oral Tablet

TABLE 1-8 Verapamil Answer Pool

Tiny Small Medium Large Dosing regimens Bioavailability answers

a 0 1.06 26 116 40 mg qd Yes