Bài tập Dược động học

IV BOLUS

1. A drug is eliminated through glomerular filtration and hepatic metabolism (no

other clearance mechanisms are observed). It does not bind to plasma proteins.
Glomerular filtration rate is normal (130 ml/min). No active renal secretion and
passive or active reabsorption after renal filtration is observed. The volume of
distribution is 50 L. When given as an i.v. bolus, plasma concentrations one hour
after administration were 5.2 mg/L. 3 hours after administration the concentration
was 2.6 mg/L. (25 pts)

5a. What is ke?

5b. What is the total clearance of the drug.

5c. What is the renal clearance of the drug?

5d. What is the hepatic clearance of the drug?

5e. After 10 doses of this drug (given once a day) the concentration two
hours after the last dose is 3.67 mg/L. What will be the concentration 10
hours later (12 hours after the last injection).

2.A 80 kg male patient was given a single i.v. dose of 45 mg cocaine which is
known to have a half-life of 0.693 hr and a volume distribution of 2 L/kg.

(1) What is the clearance of cocaine? Is it solely metabolized by liver? Why?

(2) Predict AUC0-

3.A patient is to be started on two medications (A and B) administered by IV bolus
injections. Blood samples were taken at 1 and 4 hours following the first injections
of drug A or B alone in order to determine whether concentrations were in an
appropriate range for each drug. See table below for these levels and additional
infomation

Assume liver blood flow of 90 L/h, where EH is the extraction ratio and fu is the
fraction unbound. Both drugs are metabolized by CYP 3A4
to
. Is calculate the AUC0-∞,
it possible to calculate forfordrug
the AUC0-, B, ififyes
drug B, yes
howhow
muchmuch
is it ? is it ?
if no , why not?

4.Patient H. was given 100mg of drug M intravenously. His plasma levels are
listed below. Please calculate Vd!

5.A patient was given 200mg of a low extraction drug as an IV bolus injection and plasma conce

(1) Estimate the renal clearance of this drug. (Assume there are only hepatic and
renal clearance, and hepatic clearance of this patient is 10L/h)
6. 5 mg Dexamethasone were administered to a 40-year old (75 kg) patient through
an IV bolus injection. The clearance and volume of distribution of dexamethasone
are 3.7 mL/min/kg and 0.82 L/kg, respectively. Assume a one-compartment body
model and first-order elimination.

Calculate ke, half-life (t½), and AUC

7.500 mg IV dose of getamicin is given as a short-term IV infusion to an 80kg, 52
year old, 5’5” male patient. He has a serum creatinine of 0.8mg/dL. The clearance
of this drug is equivalent to creatinine clearance.

A. Calculate the clearance.

B. Assuming this drug is only distributes into extracellular fluid and the volume of
extracellar fluid is equal to that of an average person, what is the half-life?
8.Given the following data collected after 300 mg dose and 750mg dose i.v. bolus
(Table 1) with their corresponding semi-log plots and concentration vs. time
equations (figure 1):

a) figure out the Ke, Vd, CL and AUC for each dose with appropriate units;

b) state why you can say this drug follows linear one compartment
pharmacokinetics in the given dose range by using each of the above 4 parameters.
9. A hypertensive patient is going to receive long-term medication of drug A. Drug
A can only be administered via IV-bolus injection due to its low oral
bioavailability. The volume of distribution and clearance of drug A are 120 L and
10 L/h, respectively. Drug A’s plasma protein binding is 30%. Drug A is known to
show severe side effects if its free plasma concentration is higher than 5µg/mL. In
order to avoid these side effect and to reach an antihypertensive effect, the Drug
A’s maximum free drug concentration at steady state should be 20% less than
5µg/mL. The patient has agreed to come twice a day to hospital for the
administration of the drug. The physician asks you as a clinical pharmacist to
calculate the dose that should be administered to the patient. Which assumptions
did you make to ensure that your calculations are valid?

10. Another patient receives the same drug (drug A) as a single-dose IV-bolus
injection to treat his hypertensive crisis. A metabolite of drug A is known to
counteract the effect of another drug that the patient receives. Thus, a physician
asks you as a clinical pharmacist to predict the plasma concentration of the
metabolite 6 hours after the administration of the drug A. Assume that 500 mg of
drug A will be administered and that the elimination rate constant of the metabolite
after IV-bolus injection is 5 h-1 (kmet = 0.04 h -1 , VDM = VD). Calculate the
total amount of metabolite that has been eliminated. Assume the metabolite is
solely cleared by the kidney (no further metabolism). Sketch a semi-logarithmic
plot of the plasma concentration time profile of drug A and its metabolite. Would
this sketch change tremendously if the elimination rate constant of the metabolite
was doubled? If yes, sketch the new semi-logarithmic plot of the
plasmaconcentration-time-profile.

11. A male patient (30-year old, 100kg, 5’5’’ height) was given a 400 mg IV bolus
dose of

drug X. His serum creatinine level was determined to be 1.0 mg/dL.

a) Please calculate the patient’s creatinine clearance.

b) Assume that drug X is solely eliminated via the kidneys. The volume of
distribution

of drug X is 20 L. Please calculate the half-life, , and plasma concentration

12. A drug is eliminated through glomerular filtration and hepatic metabolism. It
does not bind to plasma proteins. Glomerular filtration rate is normal. No active
renal secretion and passive or active reabsorption after renal filtration is observed.
The volume of distribution is 50 L. When given as an i.v. bolus, plasma
concentrations one hour after administration were 5.2 mg/L. 3 hours after
administration the concentration was 2.6 mg/L.

a. What is the plasma concentration 8 hours after administration of the drug?

b. 7b. What is the hepatic clearance?

13.Mr J.S., a 41 yr old, 60 kg, double amputee patient with G-ve pneumonia, was
being treated with gentamicin and ampicillin. Gentamicin had been given as an iv
bolus (0.5 mg/kg). Serum samples were obtained at 1 and 8 hours post injection,
and the lab reported concentrations of 3 and 0.5 mg/ml, respectively. Assume one
compartment, first-order elimination for gentamicin. a. Calculate ke and half-life of
gentamicin in this patient. b. Calculate Vd. Knowing that Vd in normal
subjects=0.25 L/kg, explain any observed deviations for this patient.
14.A 10 yr old, 25 kg patient suffering from Status Asthmaticus was given an iv
bolus of aminophylline (500 mg). When serum concentrations were measured at 0
and 5 hours after injection, drug levels were found to be 35 and 14.4 mg/ml,
respectively. Assume a therapeutic range of (10-20) mg/ml for theophylline, 1 mg
aminophylline is equivalent to 0.8 mg theophylline, and elimination occurs by a
first-order process. a. Calculate t1/2, ke, Vd and CL for theophylline in this patient.
b. How long will it take before the patient is subtherapeutic? c. Given the data

below calculate AUC0®¥.

15.A patient is admitted to the ER upon ingesting an overdose of theophylline. A
serum drug level was measured at 53 mg/ml. Assuming an 8 hour t1/2 and and no
further drug absorption, determine how long it would take for the serum level to
drop to the upper limit of the therapeutic range (20 mg/ml).
16. A 80 year old, 70-Kg patient with pneumonia, was being treated by an iv. bolus
of gentamicin ( 0.5 mg / kg ). Serum samples were taken at 0.5 and 6 hours post
injection, and the lab reported drug concentrations of 3.41µg/ml, and 0.83 µg/ml,
respectively. Assume gentamicin follows one compartment, first-order elimination.

1.) Calculate the half-life of gentamicin in this patient.

2.) Calculate the volume of distribution of gentamicin in this patient. 3.) Can you
predict what is the drug concentration two half-lives after iv. bolus injection?
17.A 50 year old male suffering from pneumonia was given a 1000mg IV bolus dose of the antib

18.The same patient was also given a 500mg IV bolus dose of Grebohol. His initial
plasma concentration is 10mg/L. If protein binding in the tissue is equal for both
drugs, what is the difference in plasma protein binding between the two? (use a
plasma volume of 3L and a tissue volume of 38L)
19.Patient H.G. was given 1000mg drug X as an i.v. bolus. Determined plasma
concentration-time profiles are listed in the table below.

a) Determine whether the drug follows a zero- or a first-order elimination

process!

b) Calculate the elimination rate constant (ke)!

c) Calculate AUC0Æ! d) Can you predict what the concentration of drug X after two half-lives w