Name: _____________________ UFID: _____________________

PHA 5128 Spring 2009

First Exam (Version B) On my honor, I have neither given nor received unauthorized aid in doing this assignment. Print: _________________________________________________________________ Sign:__________________________________________________________________

Version B

Q1: Phenytoin (10)

Q2: procainamide (10)

Q3: digoxin (10)

Q4: vancomycin (10)

Q5: Age (5)

Q6: gentamicin (10)

Q7: CL (5)

Q8: valproic acid (10)

Q9: Digoxin (10)

Q10: carbamazepine (10)

Q11: Methotrexate (10)

Total Points: 100

Question 1:

P.T., a 35-year-old, 74 kg male, had been taking 300 mg/day of phenytoin; However, his dose was increased to 350 mg/day because his seizures were poorly controlled and because his plasma concentration was only 7 mg/L. Now he complains of minor CNS side effects and his reported plasma phenytoin concentration is 22 mg/L. Renal and hepatic function are normal. Assume that both of the reported plasma concentrations represent steady state levels and that P.T. has complied with the prescribed dosing regimens. Calculate P.T.’s apparent Vm and Km.

A. Vm = 380 mg Km = 1.9 mg/L B. Vm = 1.9 mg Km = 380 mg/L C. Vm = 760 mg Km = 0.9 mg/L D. Vm = 0.9 mg Km = 760 mg/L E. None of the above

Initially, 

7= Km * 300/ (Vm ‐300) 

7Vm  ‐2100 = Km * 300 ‐‐‐‐‐‐‐1 

 

Changed 

22= Km * 350/ (Vm ‐350) 

22Vm  ‐7700 = Km * 350‐‐‐‐‐‐‐2 

 

Solving 1and 2 

Vm = 379.5 ~ 380 mg 

And then  

Km = 1.86 ~ 1.9 mg/L 

Question 2:

B.K., a 65-year-old, 75 kg male, was admitted to the coronary care unit with a diagnosis of acute myocardial infarction. He has a history of mild chronic renal failure, but he does not have CHF. His serum creatinine of 1.5mg/dL. He has developed premature ventricular contractions (PVCs) which were unresponsive to lidocaine. Calculate a parenteral loading dose of procainamide designed to achieve a plasma concentration of around 8 mg/L and an i.v. maintenance infusion rate that will maintain an average plasma concentration of 6mg/L.

A. Loading Dose = 1200 mg; Maintenance infusion rate = 184 mg/min B. Loading Dose = 1200 mg; Maintenance infusion rate = 3.1 mg/min C. Loading Dose = 1400 mg; Maintenance infusion rate = 184 mg/min D. Loading Dose = 1400 mg; Maintenance infusion rate = 3.1 mg/min E. Loading Dose = 1200 mg; Maintenance infusion rate = 21.4 mg/hr

Vd= 2* 75 = 150 L LD =Cp * Vd / (F * S) = 8 * 150/ (1 * 0.87) = 1379 mg ~ 1400 mg Clcr = (140-65) * 75/ ( 72 * 1.5)= 52.1 ml /min ~ 3.1 L/h Clren = 3 * 3.1 = 9.3 L/h Clacet = 0.13 * 75 = 9.75 L/h Clother = 0.1 * 75 = 7.5 L/h Cltotal = 9.3 + 9.75 + 7.5 = 26.65 L/h MD = Cssave * CL * τ /( F* S) = 6 * 26.65 * 1 / ( 1 * 0.87) = 183. 8 mg/hr ~ 184 mg/hr ~ 3.1 mg/min

Question 3:

A.H. (55 years old, 58 kg, SrCr = 2.5 mg/dL, female) was admitted to the

hospital and was diagnosed with congestive heart failure. She had been taking

0.25 mg digoxin qd for 3 months. The digoxin plasma concentration was

determined to be 5 μg/L. How long will it take for the concentration to fall back to

1 μg/L if digoxin therapy was stopped? Pick the closest answer. (10 points)

A. 2 days B. 4 days C. 8 days D. 16 days E. 31 days

Clcr (female) = (140-55)* 58 / (85* 2.5) = 23.2 ml/min Cl ( CHF patients) = (0.33 *58) + (0.9 *23.2) = 40.0 ml/min ~ 57.6 L/day V = (3.8 * 58) + (3.1 * 23.2) = 292 L k = Cl /V = 57.6 /292 = 0.197 day -1

t = ln (C1/C2)/ k = ln (5/1)/ 0.197 = 8.15 days

Question 4:

H.K., 55 year old, 5’2”, 70 kg woman with a serum creatinine of 1.6 mg/dL, has been empirically started on 500 mg of vancomycin every 12 hours for treatment of a staphylococcal infection. What are the expected peak and trough vancomycin concentrations for H.K? (10 points). (Use IV Bolus Equations).

A. Css max =26 mg/L Css min = 13.5 mg/L B. Css max =52 mg/L Css min = 27 mg/L C. Css max =13 mg/L Css min = 6.8 mg/L D. Css max =10 mg/L Css min = 5 mg/L E. Css max =13.5 mg/L Css min = 26 mg/L

First, the Vd, Cl and ke must be calculated: For the Vd, Vd =0.17(55 years) + 0.22 (70 kg) + 15 = 39.75 L Creatinine clearance can be used to estimate her clearance, but we must first check if the patient is obese: IBW=45.5+2.3*2=50.1 IBW*1.2=50.1*1.2=60.12 Since the patient is obese, we use the ABW for the CL calculation: ABW=IBW + 0.4(TBW-IBW)=50.1 + 0.4(19.9)=58.06 Clcr = (140-55)*58.06 = 36.29 mL/min = 2.18 L/h ~Cl 85*1.6 Now ke can be determined: Ke = 2.18/39.75 = 0.055 h

-1

Now you can determine peak and trough concentrations Css max = (500/39.75) = 26.03 mg/L

(1 - e -0.055*12

) Css min = 26.03*e

-0.055*12 = 13.45 mg/L

Question 5: Which combination of the following pharmacokinetic changes best describes the elderly and neonates? (These groups share similar PK characteristics.)

1. Low renal clearance 2. Longer half-lives 3. Low metabolic clearance 4. Decreased protein binding 5. Relatively less body water

A. 1 & 4 B. 1, 2, 3& 4 C. 1, 3, 4 &5 D. 1, 4, &5 E. all of the above

Question 6:

A patient was given 100 mg gentamicin over 30 minutes (i.v.) from 8:30 to 9:00 am. The following two serum levels were measured: 6μg/ml at 9:30 am and 2μg/ml at 4:00 pm. Calculate:a.the peak concentration at 9:00 am, b.the volume of distribution. (assume steady state levels)

A. a:6.53 ug/ml, b:19.8L B. a:12.84ug/ml, b: 39.6L C. a:6.53 mg/ml, b:22.2L D. a: 12.84ug/ml, b:39.6L E. a: 25.9 mg/L, b: 65 L

   

   

Question7: Which of the following changes goes along with a decreased clearance and no change in volume of distribution?

A. shorter half-life, higher steady state concentration B. longer time to steady state, shorter half-life C. longer time to steady state, lower steady state concentration D. increased initial concentration after an i.v. bolus, longer time to steady state E. longer time to steady state, higher steady state concentration

Question 8:

C.S., a 10-year-old, 28 kg female, is receiving valproic acid sprinkles 250 mg (2×125mg) po q8hr for her seizure disorder. Calculate her valprioc aicd level at steady state.

A. Cpss_ave= 63mg/L B. Cpss_ave= 72mg/L C. Cpss_ave= 80mg/L D. Cpss_ave= 86mg/L E. Cpss_ave= 94mg/L

  Cl = (13mL/kg/hr)(28kg) = 364mL/hr or 0.364L/hr 

   

Cpss_ave= (1)(1)(250mg/8hr)/(0.364L/hr) = 85.85 mg/L 

Question 9:

Please mark the CORRECT statements about Digoxin.

1) Digoxin is a PGP-substrate. 2) Digoxin follows a one compartment body model. 3) Digoxin levels are increased in patients with hyperthyroid function. 4) Digoxin distributes rapidly into the myocardial tissue. 5) Digoxin is only renally eliminated

A. 1, 3, 4 B. 2, 3, 5 C. 1, 2, 3, 4 D. 1, 2, 4, 5 E. None of the above

Question 10:

Y.T., a 46-year-old, 60 kg female, is to be given carbamazepine as an anticonvulsant agent. Calculate a daily dose of Tegretol XR that will produce an average steady-state plasma concentration of approximately 8mg/L. What would be a reasonable starting dose?

A. MD = 800mg/day, start with 200mg twice daily and increase by 200 mg/day in weekly intervals

B. MD = 600mg/day, start with 200mg daily and increase by 200 mg/day in weekly intervals

C. MD = 600mg/day, start with 300mg twice daily D. MD = 1000mg/day, start with 200mg twice daily and increase by 200 mg/day in weekly

intervals E. MD = 1000mg/day, start with 500mg twice daily

, 8 .064 60 24 1053 / 1000 /0.7 1

ss aveC CLMD mg day mg day

F Sτ⋅ ⋅ • • •

= = = ≈⋅ •

 

 

Start with 200mg twice daily and increase by 200 mg/day in weekly intervals until the final dose of 

1000mg/day. 

Questions 11:

T.X. is a 53 kg female patient (47 years) to receive methotrexate therapy. Her serum creatinine is 1.2 mg/dL. She is treated with a loading dose (20 mg) followed by an infusion of 25 mg/h over 36 hours. She will then receive a 10 mg/m2 dose of leucovorin q6h (four doses) followed by eight oral doses (q6h) of 20 mg. Calculate the expected MTX concentration at 60hr after the start of the infusion and the expected time that the methotrexate level will fall below 0.1 μM by using the typical half-life parameters? After the drug sampling report [14 μM (24h), 1.74 μM (48 h), and 0.20 μM (75h)], adjust your prediction according to data. (You can assume the plasma concentration already reached steady state after 24 hrs infusion.)

A. Expected: C60h=0.24uM, t0.1uM=73 hr; Adjusted: C60h=0.40uM, t0.1uM=90 hr B. Expected: C60h=0.40uM, t0.1uM=80 hr; Adjusted: C60h=0.45uM, t0.1uM=85 hr C. Expected: C60h=0.75uM, t0.1uM=88 hr; Adjusted: C60h=0.55uM, t0.1uM=82 hr D. Expected: C60h=0.40uM, t0.1uM=80 hr; Adjusted: C60h=0.65uM, t0.1uM= 88hr E. Expected: C60h=0.15uM, t0.1uM=68 hr; Adjusted: C60h=0.32uM, t0.1uM=108 hr F. Calculate the expected MTX steady-state concentration (in µM).

( )140 47 5348.3 / min 2.9 /

85 1.2CrCL mL L h− ⋅

= = ≈⋅

 

1.6 2.9 / 1.6 4.64 /MTX CrCL CL L h L h= ⋅ = ⋅ =  

0 25 / 5.39 /5.39 / 11.874.64 / 0.454ss

R mg h mg LC mg LCL L h

= = = = = uM  

 

Calculate the predicted concentrations at 24, 48 and 60 h after the start of the MTX infusion.

36 h: 11.87 µM

0.5

11.87ln0.5 36 13.7 36 49.7

0.231uMt h

⎛ ⎞⎜ ⎟⎝ ⎠= + = + =

60 h: 0.0693 (60 49.7)0.5 0.24Cp uM e uM− ⋅ −= ⋅ =

0.1

.5ln0.1 49.7 72.9

0.0693µMt h

⎛ ⎞⎜ ⎟⎝ ⎠= + =

The reported levels were 14 μM (24h), 1.74 μM (48 h), and 0.20 μM (75h)

1

14ln1.74 0.17412

k hα−

⎛ ⎞⎜ ⎟⎝ ⎠= =

0.5

14ln0.536 55.2

0.174uMt h

⎛ ⎞⎜ ⎟⎝ ⎠= + =

1

1/ 2 0.1

0.5ln( )0.2 0.0463

75 55.215 60 0.4 90uM

k h

T h Cp uM and t h

β

β

−= =−

= ⇒ = =