Pharmacokinetics: A Refresher Flashcards
1
Q
- J.H., a 65-year-old woman (weight 65 kg), was
recently initiated on tobramycin and piperacillin/
tazobactam for the treatment of hospital-acquired
pneumonia.Afterthefirsttobramycindoseof120mg
(infused from noon to 1:00 p.m.), serum tobramycin
concentrations are obtained. They are 4.4 mg/L at
3:00 p.m. and 1.2 mg/L at 7:00 p.m. Which is the
best assessment regarding the calculation of tobra-
mycin pharmacokinetic parameters in this patient?
A. Data are sufficient to determine the half-life
but not the volume of distribution (Vd).
B. Data are sufficient to determine both the half-
life and the Vd.
C. Data are insufficient to determine either the
half-life or the Vd.
D. Data are sufficient to determine the Vd but not
the half-life.
A
- Answer: B
With two concentrations, data are sufficient to calculate
an elimination rate constant and, therefore, a half-life
(Answers C and D are incorrect; Answer B is correct).
In addition, the Vd can be calculated by back extrap-
olation to the Cmax and use of appropriate equations
(because this was the first dose, and therefore it is
known that the tobramycin concentration was 0 mg/L
before the dose was given) (Answer A is incorrect and
Answer B is correct).
2
Q
- P.L. is a 60-year-old woman (60 kg) recently initi-
ated on gentamicin and clindamycin. After the first
gentamicin dose of 110 mg (infused from 6:00 p.m.
to 6:30 p.m.), serum gentamicin concentrations
are obtained. They are 3.6 mg/L at 7:30 p.m. and
0.9 mg/L at 11:30 p.m. Which is the best assess-
ment of this patient’s gentamicin pharmacokinetic
parameters?
A. The half-life is about 2 hours.
B. The half-life is about 3 hours.
C. The maximum concentration (Cmax) is about
3.8 mg/L.
D. The Vd is about 11.6 L.
A
- Answer: A
The elimination rate constant equals (ln 3.6 mg/L
− ln 0.9 mg/L)/4 hours = 0.35/hour. The half-life is
0.693/0.35 = 2 hours. The concentration at the end of
the infusion equals 3.6 mg/L/e – (0.35 * 1) = 5.1 mg/L.
The patient’s Vd = dose/change in concentration, or
110 mg/5.1 mg/L = 21.5 L (Answer A is correct;
Answers B, C, and D are all incorrect)
3
Q
- R.O. is a 74-year-old woman initiated on gentamicin
100 mg intravenously every 24 hours for pyelone-
phritis. On admission, her serum creatinine (SCr)
is 1.8 mg/dL. She has heart failure and is fluid over-
loaded because of her diminished renal function,
and she is nonadherent to her angiotensin-converting
enzyme inhibitor and diuretic. A few days into
her hospitalization, her SCr is down to 1.1 mg/dL,
and she is reinitiated on furosemide and enalapril.
Which most likely happened to the gentamicin
half-life in R.O. during her hospitalization?
A. Her clearance increased, which increased her
Vd and decreased her half-life.
B. Her clearance increased, which increased her
elimination rate constant and decreased her
half-life.
C. Her Vd decreased, which increased her clear-
ance and decreased her half-life.
D. Her Vd decreased, which increased her elimi-
nation rate constant and increased her half-life.
A
- Answer: B
Her clearance increased because of the improvement
in renal function, which increased her elimination rate
constant and decreased her half-life (Answer B is cor-
rect). The Vd would not be altered by changes in clear-
ance (they are independent) (Answer A is incorrect).
With the diuresis and angiotensin-converting enzyme
inhibitor, her Vd probably decreased, but clearance
would not be altered by changes in Vd (they are inde-
pendent) (Answer C is incorrect). In addition, if her Vd
decreased, her half-life would decrease, not increase
(Answer D is incorrect).
4
Q
- A patient receives vancomycin 1000 mg intrave-
nously every 24 hours and has a trough concentra-
tion, obtained 30 minutes before the next dose, of
6 mg/L, with an estimated vancomycin 24-hour
AUC of 210 mg * hour/L. Which regimen is best
for this patient if the goal AUC/MIC is 400–600
(assuming an MIC of 1 mg/L)?
A. Maintain the dosage at 1000 mg intravenously
every 24 hours.
B. Lower the dosage to 500 mg but keep the inter-
val at every 24 hours.
C. Keep the dosage at 1000 mg but shorten the
interval to every 12 hours.
D. Lower the dosage to 500 mg and shorten the
interval to every 12 hours.
A
- Answer: C
Because the trough and AUC/MIC are too low, the inter-
val will have to be shortened to increase the concentra-
tion (Answers A and B are incorrect). Maintaining the
total daily dose will not increase the AUC/MIC to the
appropriate range (Answer D is incorrect). Vancomycin
largely has linear PK. In the absence of changes to clear-
ance and volume, doubling the dose in a 24-hour period
will double the exposure (AUC). Therefore, increasing
from 1000 mg daily to 1000 mg every 12 hours will
increase the AUC/MIC from 210 to 420 (Answer C is
correct).
5
Q
- R.K., a 39-year-old man who is HIV positive,
receives a diagnosis of cryptococcal meningitis
and begins taking amphotericin B and flucytosine. You want to keep flucytosine peak concentrations
at 50–100 mg/L. Assuming a steady-state trough
concentration of 25 mg/L, dosing every 6 hours,
and 100% bioavailability, which is the best dosage
to achieve a peak concentration within the desired
range (flucytosine volume of distribution of 0.7 L/
kg and half-life of 3 hours)?
A. 12.5 mg/kg.
B. 37.5 mg/kg.
C. 75 mg/kg.
D. 150 mg/kg.
A
- Answer: B
To achieve flucytosine peak concentrations of 50–100
mg/L. (assuming a trough concentration of 25 mg/L.,
dosing every 6 hours, and 100% bioavailability; flucy-
tosine volume of distribution of 0.7 L/kg; half-life of
3 hours), the concentration must be changed by 25–75
mg/L. Using the equation ΔCp = dose/V, a dosage of
12.5 mg/kg would increase the concentration by only
17.8 mg/L. A dosage of 75 mg/kg would increase the
concentration by 107 mg/L., whereas a dosage of
150 mg/kg would increase the concentration by 214
mg/L. The correct dosage is 37.5 mg/kg because it would
increase the concentration by 53.6 mg/L. (Answer B is
correct; Answers A, C, and D are all incorrect).
6
Q
- L.R. is a 49-year-old patient with diabetes mellitus
and renal failure on hemodialysis. He was recently
in a car accident and sustained a head trauma. He
currently receives phenytoin 100 mg intravenously
three times a day, and his most recent concentra-
tion was 5.6 mg/L. You are asked to suggest a new
dosage to achieve a concentration within the ther-
apeutic range. Laboratory results include sodium
145 mEq/L, potassium 3.9 mEq/L, chloride 101
mEq/L, carbon dioxide 26 mEq/L, blood urea
nitrogen (BUN) 95 mg/dL, SCr 5.4 mg/dL, glucose
230 mg/dL, and albumin (Alb) 2.8 g/dL. Which is
the best recommendation?
A. Increase the dosage to 200 mg intravenously
three times a day.
B. Increase the dosage to 200 mg intravenously
two times a day.
C. Decrease the dosage to 100 mg intravenously
two times a day.
D. Keep the dosage the same.
A
- Answer: D
Because of the patient’s renal failure and low Alb, the
total concentration must be corrected. The patient’s cor-
rected phenytoin concentration is 14.9 mg/L (Cp = 5.6/
{[0.48 x 0.9 x (2.8/4.4)] + 0.1} = 14.9 mg/L). Therefore,
no changes should be made to the dosage (Answer D is
correct; Answers A, B, and C are all incorrect).
7
Q
- You are asked how the fluorescence polariza-
tion immunoassay (TDx) and enzyme multiplied
immunoassay technique (EMIT) assays compare
with each other. Which statement is most accurate?
A. Although both are immunoassays, one uses
antibodies to bind the molecule of interest,
whereas the other uses antigens.
B. Although both are immunoassays, one uses an
enzyme label, whereas the other uses a radio-
isotope label.
C. Although both are immunoassays, one uses an
enzyme label, whereas the other uses a fluo-
rescent label.
D. They are both names for the same assay
technique.
A
- Answer: C
Both of these are immunoassays but they are different
(Answer D is incorrect). Because they are both immu-
noassays, they both use antibodies to bind the molecule
of interest (Answer A is incorrect). A brand name for
the Abbott fluorescence polarization immunoassay is
TDx, which uses a fluorescent label. The term EMIT
stands for enzyme multiplied immunoassay technique,
which is an immunoassay that uses an enzyme label
(Answer C is correct). Neither of them use radioiso-
topes (Answer B is incorrect).
8
Q
- An older adult is seen in the morning medicine
clinic for a routine follow-up. Medication history
includes digoxin 0.25 mg/day by mouth, furose-
mide 40 mg/day by mouth, and potassium chloride
10 mEq/day by mouth. All doses were last taken
at 8:00 a.m. today at home. The patient has vague
complaints of stomach upset, which began 2 days
ago, but is otherwise in no apparent distress. A
serum digoxin concentration obtained today at
10:00 a.m. is 2.5 mcg/L. Which statement best
describes what should be done next?
A. Admit the patient for administration of digoxin
Fab.
B. Tell the patient to skip tomorrow’s dose of
digoxin and begin 0.125 mg/day by mouth.
C. Administer a dose of activated charcoal.
D. Do nothing today with the digoxin.
A
- Answer: D
The digoxin concentration was obtained too close to the
8:00 a.m. dose. The digoxin had not yet had a chance
to complete its distribution phase. Once distribution
is complete (generally 6–12 hours after the dose), the
concentration will be lower and probably within the
therapeutic range (Answer D is correct). Therefore,
there is no need for the digoxin antibody (Answer A is
incorrect), activated charcoal (Answer C is incorrect),
or lowering of the dosage (Answer B is incorrect).
9
Q
- A research group is analyzing the relationship
between various independent patient demograph-
ics (e.g., age, height, weight, albumin, creatinine
clearance [CrCl]) and phenytoin pharmacokinetics.
Which is the best statistical test to use in assessing
the relationship?
A. One-way analysis of variance.
B. Analysis of covariance.
C. Multiple regression.
D. Spearman rank correlation.
A
- Answer: C
The correct statistical test is multiple regression.
Multiple regression is used to describe the relationship
between a dependent variable and two or more inde-
pendent variables when both the dependent and inde-
pendent variables are numeric (Answer C is correct).
Analysis of variance is used to describe the relationship
between a dependent variable and two or more indepen-
dent variables when the dependent variable is numeric
and the independent variables are nominal (Answer A
is incorrect). Likewise, analysis of covariance is used to
describe the relationship between a dependent variable
and two or more independent variables when the depen-
dent variable is numeric and the independent variables
are nominal with confounding factors (Answer B is
incorrect). Spearman rank correlation is a nonparamet-
ric test used to describe the relationship between one
dependent and one independent variable when the data
are ordinal or numeric and not normally distributed
(Answer D is incorrect).
10
Q
- N.T. is a 24-year-old woman receiving valproic acid
for tonic-clonic seizures. Her most recent trough
valproic acid concentration was 22 mg/L. Her
most recent albumin concentration was 4.1 g/dL.
Given this albumin, which recommendation is best
regarding her dosage?
A. Continue with the current dosage; the concen-
tration is close enough to the therapeutic range.
B. Assess adherence and increase her dosage; the
concentration is below the therapeutic range.
C. Decrease her dosage; the concentration is
slightly above the therapeutic range.
D. Assess adherence and then check a free valproic
acid concentration and adjust accordingly.
A
- Answer: B
Assessing adherence and increasing her dosage is the
best recommendation, because the concentration is
below the therapeutic range (Answer B is correct). The
valproic acid therapeutic range is 50–100 mg/L, and
she is well below this concentration. Although some
patients are controlled at lower concentrations, this
concentration is probably too low (Answer A is incor-
rect). She definitely does not need a decrease in dosage
(Answer C is incorrect). Although total valproic acid
concentrations are affected by changes in Alb, her Alb
is normal, and obtaining a free concentration is unnec-
essary (Answer D is incorrect).
11
Q
- N.G. is a 54-year-old woman with a recent head
injury. She comes to your pharmacy with com-
plaints about the prescription for acetaminophen
with codeine you dispensed to her yesterday. She
says that it does not seem any stronger than when
she uses acetaminophen alone. On her profile, you
notice results from pharmacogenomics testing per-
formed 3 years ago that shows she is a CYP2D6
poor metabolizer. In addition to acetaminophen
and codeine, she is receiving aspirin, clopidogrel,
omeprazole, lisinopril, citalopram, metoprolol
succinate, docusate, and trazodone. Which is the
best explanation why N.G. does not seem to benefit
from codeine?
A. Omeprazole inhibited CYP2C19, causing less
codeine activation.
B. Codeine is not as active in N.G. because of her
genetic profile.
C. Codeine is metabolized faster in N.G., leading
to lower concentrations.
D. Metoprolol inhibited CYP2C9, causing less
codeine activation.
A
- Answer: B
Codeine’s activity is due primarily to its metabolism
to morphine by CYP2D6 after administration. Because
this patient is a CYP2D6 poor metabolizer, less of
the codeine will be metabolized to its active metabo-
lite (Answer B is correct and Answer C is incorrect).
Omeprazole does inhibit CYP2C19, but this enzyme
does not metabolize codeine (Answer A is incorrect).
Metoprolol is a substrate of CYP2D6 but is not an
inhibitor or inducer of CYP2C9 Answer D is incorrect).
12
Q
- At your hospital you are responsible for making
dosing adjustments in patients with poor renal
function. While working with you, a student asks
why you are using the Cockcroft-Gault method for
estimating CrCl instead of the newer Modification
of Diet in Renal Disease (MDRD) or Chronic
Kidney Disease Epidemiology Collaboration
(CKD-Epi) equations. Which is the best response
to provide to this student?
A. MDRD and CKD-Epi are not as good esti-
mates of renal function and may lead to inap-
propriate changes in drug dosing.
B. MDRD and CKD-Epi were developed in an
ambulatory care population and cannot be
used for hospitalized patients.
C. The Cockcroft-Gault estimate of CrCl has
units that are different from the glomerular
filtration rate estimates calculated using the
MDRD and CKD-Epi equations.
D. Recommendations for renal dosing adjust-
ments in package inserts are usually based
on CrCl estimates using the Cockcroft-Gault
equation.
A
- Answer: D
The MDRD and CKD-Epi are actually better esti-
mates of renal function because they directly esti-
mate GFR instead of CrCl (Answer A is incorrect).
Although the Cockcroft-Gault equation was developed
in hospitalized patients and the MDRD and CKD-
Epi equations were developed in ambulatory patients,
this does not affect the setting where they can be
used (Answer B is incorrect). Moreover, although the
equations do have different units (mL/minute vs. mL/
minute/1.73 m2
), this can easily be corrected by con-
verting the result of the MDRD or CKD-Epi equation to
milliliters per minute (Answer C is incorrect). The best
reason for not using MDRD or CKD-Epi for drug dos-
ing is that renal dosing adjustment recommendations
published in package inserts are almost always based
on CrCl estimates using the Cockcroft-Gault equation
(Answer D is correct).
13
Q
- An assay used for therapeutic drug monitoring at
your institution has a low sensitivity and low preci-
sion. Which is the best statement about the impact
of this assay on drug monitoring?
A. The assay may be unable to detect concentra-
tions that are therapeutic, and it will report
highly variable values when repeatedly run on
the same sample.
B. The assay may be unable to detect concen-
trations that are therapeutic, and it will con-
sistently over- or under-measure the true
concentration.
C. The assay will be unable to differentiate
between like substances, and it will con-
sistently over- or under-measure the true
concentration.
D. The assay will be unable to differentiate
between like substances, and it will report
highly variable values when repeatedly run on
the same sample.
A
- Answer: A
Assays with low sensitivity will not be able to detect
low drug concentrations, which may still be therapeutic
(Answer A is correct). Assays that cannot differentiate
between like substances have low specificity (Answers
C and D are incorrect). Assays that report highly vari-
able values when repeatedly run on the same sample
have low precision (Answer A is correct). Assays that
consistently over- or under-measure the true concentra-
tion have low accuracy (Answers B and C are incorrect).
