TEST YOUR KNOWLEDGE
OF MATERIAL COVERED IN
PHARMACOKINETICS AND BIOPHARMACEUTICS (46:138)
To assist you in testing your knowledge of the material covered in the class, a series of questions have been posted. Each question has a link to an answer. The questions are not in any particular order in terms of the topics, but the lectures associated with each question are indicted in red after the question. You will obtain the most benefit from these questions by attempting to answer them on your own before looking at the answer.
1.
Below is shown the absorption rate constant (ka)
for three different preparations of a drug. Identify which preparation will
give the fastest onset of action and which will give the lowest intensity of
pharmacologic effect.
Preparation ka
(hr-1)
A 0.2
B 0.3
C 0.4
(Determinants
of Pharmacologic Effect Lecture)
2.
A group of subjects is
administered PHC138 as a sublingual (SL) tablet and as an oral rapid release
preparation (identical doses administered with each route). Though the plasma
concentrations of PHC138 after SL administration are substantially higher than
those found after oral administration, the intensity and duration of
pharmacologic effect are greater following oral administration. Provide a
plausible explanation for this observation.
(Effect of
Route of Administration on Drug Disposition and Action Lecture)
3. If a drug which is
poorly water soluble is given as a single oral or single intramuscular dose,
which route will provide the longest duration of action?
(Effect of Route of Administration on Drug Disposition and Action Lecture)
4. JT is a 31 year old diabetic who has experienced significant problems with gastric reflux. He also suffers from arthritis and takes enteric coated aspirin for arthritis pain. As a treatment for his gastric reflux, JT is placed on metocloporamide, and agent which increases the rate of gastric emptying. What effect would the addition of metoclopramide to this patient's regimen have on the onset, duration, and intensity of the aspirin therapy he is also receiving?
(Effect of Route of Administration on Drug Disposition and Action & Determinants of Pharmacologic Effect Lecture)
5. Administration of an enzyme inducer that increases the metabolism of a drug that is subject to significant first-pass metabolism and is administered orally would be expected to have the greatest impact on which measure of pharmacologic effect (compared to the drug given orally without the enzyme inducer)?
(Effect of Route of Administration on Drug Disposition and Action Lecture)
6. Amonafide is an
investigational agent being evaluated for the treatment of solid tumors. The
dose-limited toxicity with amonafide is myelosuppression. Amonafide is
metabolized to N-acetylamonafide. A recent study compared the hematologic
effects of amonafide in a group of patients based on their acetylator status.
The mean lowest white blood cell count in slow acetylators receiving amonafide
was 3,400 per microliter, while that in fast acetylators was 500 per microliter.
Similarly, the mean lowest absolute neutrophil count in slow acetylators was
1,638 per microliter, while that in fast acetylators was 49. Based on these
observations:
a) Is a patient's
acetylator status a predisposing factor to the development of myelosuppression
during treatment with amonafide?
b) Which group is at
greatest risk for developing myelosuppression?
c) If both
myelosuppression and tumor killing activity were due to the same species (drug
or metabolite), should the dose of amonafide in slow acetylators be lower or
higher than that in fast acetylators.
(Pharmacogenetics Lecture)
7.
From the data below, identify the likely mechanism of
absorption of this agent.
|
Dose (mcg) |
Amount Absorbed (mcg) |
|
0.5 |
0.4 |
|
2.0 |
0.9 |
|
5.0 |
1.3 |
|
10 |
1.5 |
|
50 |
2.0 |
|
200 |
3.3 |
|
500 |
6.0 |
(Passage of Xenobiotics Across Biological Membranes)
8. Nelfinavir is a protease inhibitor used in the
treatment of HIV infection. Studies have demonstrated that it is a substrate
for the efflux pump, p-glycoprotein. If nelfinavir is given together with an
inhibitor of p-glycoprotein, would you anticipate that the CNS:plasma
concentration ratio would increase or decrease, compared to nelfinavir alone?
(Distribution
of Xenobiotics Lecture)
9. MK422 is a new agent for the treatment of erectile
dysfunction undergoing clinical trials. After the introduction of Viagra, there
have been reports of an increased incidence of death in men with coronary
artery disease taking Viagra. As a consequence, the FDA has requested that the
manufacturer of MK422 conduct a study to evaluate the safety and efficacy of
MK422 in patients with coronary artery disease. While the safety of MK422 was
confirmed in this study, there was found to be an increased incidence of treatment
failures. Subanalysis of the study revealed that most patients who failed to
receive benefit with MK422 were also receiving quinidine. Metabolic studies
demonstrated that MK422 is eliminated approximately 50% by hepatic metabolism,
and that almost solely via CYP2D6. What does this information tell you about
MK422?
(Pharmacogenetics
Lecture)
10.
Drug X is metabolized to a single metabolite via
CYP3A4. This metabolite is found to be equipotent to Drug X. After
administration of a single dose of drug X, the apparent half-life of both X and
its metabolite were found to be 8 hr. However, when clinical studies were conducted
with the metabolite alone, the pharmacologic effect of the metabolite was found
to be of shorter duration than that of drug X. Provide a possible explanation
for this observation.
(Metabolite
Kinetics Lecture)
11.
Drug A is administered as a racemic mixture. The renal
clearance of the (+) isomer is 90 mL/min, while that of the (-) isomer is 50
mL/min. Changing urine flow does not alter the renal clearance of either
isomer. Provide a possible mechanism for the difference in renal clearance
between these two isomers.
(Stereochemistry
Considerations in Drug Disposition Lecture)
12. Draw a plot showing the relationship
between Vss (y-axis) and fup (x-axis).
(Pharmacokinetics
– Noncompartmental Analysis Lecture)
13. Draw a plot showing what
happens to Vss (y-axis) as CL(x-axis) increases.
(Pharmacokinetics – Noncompartmental Analysis Lecture)