Jashore University of Science and Technology

Department of Pharmacy
Course Title: Clinical Research and Pharmacokinetics - II
Course Code: PHAR-5207

An assignment
On
Questionnaire made according to the contents of clinical
research and pharmacokinetics-II

Submitted by Submitted to
Name: Abir Hasan Sajid Md. Ashraful Alam
Student ID: 181035 Lecturer
5th Year, 2ndSemester Department of Pharmacy,
Session: 2018-19 Jashore University of Science and
Department of Pharmacy, Technology
Jashore University of Science and
Technology

Date of Submission: 04-02-2025

➢ What are the major differences between IV bolus and Iv infusion?

➢ How does apparent volume of distribution affect drug concentration in plasma?

➢ “Drug elimination is a First order process”- Justify the statement.

➢ How does renal impairment affect elimination rate constant?

➢ What factors determine whether a drug follows one, two or three compartmental model?

➢ “Obtaining accurate urinary excretion data is challenging task”- Explain.

➢ How can you calculate K From urinary excretion data?

➢ A patient receives a 200 mg IV bolus dose of a drug. After 6 hours, the plasma drug

concentration is 1.5 mg/100 ml. Assuming the apparent volume of distribution is 10% of

body weight (80 kg), compute the total amount of drug in the body fluids after 6 hours.

➢ Why is urinary excretion data important for calculating pharmacokinetic parameters?

➢ How does drug distribution differ between the one-compartment and two-compartment

models?

➢ If a drug has a very short half-life, would IV bolus or IV infusion be a better choice?

Why?

➢ Why is the body divided into compartments rather than using anatomical regions in

pharmacokinetics?
 Chapter 2: Kinetics Following iv infusion
Questions:

➢ Why and when will you choose IV infusion instead of IV bolus?

➢ How does IV infusion help in maintaining stable plasma drug levels compared to oral

or intramuscular administration?

➢ “Increasing the infusion rate change the steady state concentration but not the time

required to reach it”- Justify the statement.

➢ Why is it critical to control the infusion rate in drugs with a narrow therapeutic window

like heparin or vancomycin?

➢ Why does IV infusion follow zero-order input but first-order elimination?

➢ Explain why it takes about 5 half-lives for a drug to reach steady state during IV

infusion.

➢ How can the elimination half-life of a drug be determined from its steady-state

concentration (CSS)?

➢ If a drug has a very long half-life, how can you ensure a patient reaches the therapeutic

level quickly without waiting for multiple half-lives to pass?

➢ A patient asks why they can’t just receive a single high IV dose instead of a prolonged

infusion. How would you explain this using pharmacokinetic principles?

➢ A patient needs to maintain a plasma drug concentration of 15 µg/ml. If the volume of

distribution (VD ) = 20 L and the elimination rate constant (k) = 0.1 hr−1, calculate the

required infusion rate (R).

this change affect the steady-state concentration (CSS)? Will the drug reach steady-state

faster?

➢ A drug is administered via IV bolus to achieve an immediate effect, but it is also given as

a continuous infusion to maintain steady plasma levels. Why is this dual strategy useful

in clinical practice?

➢ A drug is infused at 2 mg/hr, with a half-life of 3 hours and VD = 10 L. What is the

plasma concentration after 6 hours?

➢ A critically ill patient needs an immediate plasma concentration of 20 µg/ml. If the drug’s

VD = 8 L, what should be the loading dose?

➢ If the infusion rate is doubled, how will CSS and time to steady state change?

➢ Two patients receive the same drug, but one at 5 mg/hr and the other at 10 mg/hr.

Compare their CSS and time to steady state.

➢ A drug has a half-life of 4 hours. How long will it take to reach 90% of steady state?

Chapter 3: Kinetics following extravascular administration

Questions:

➢ Why is drug absorption more complex in extravascular administration compared to IV

administration?

➢ What are the key physiological factors that influence the rate of drug absorption in the

gastrointestinal tract?
➢ Compare the pharmacokinetics of drugs that follow zero-order absorption versus first-

order absorption. Provide an example of each.

➢ Time to reach maximum plasma concentration (tmax) depends only on the absorption

and elimination rate constants and not on the drug dose. Justify the statement.

➢ A drug administered orally is highly susceptible to first-pass metabolism. How would

this affect its bioavailability (F) and plasma concentration-time curve?

➢ How do controlled-release dosage forms modify drug absorption kinetics? Would they

follow zero-order or first-order absorption? Explain.

➢ During the absorption phase of an oral drug, elimination is also occurring. Why does the

plasma drug concentration still increase during this phase?

➢ A patient takes a tablet, but the effect is delayed for 2 hours. Explain what might be

happening in terms of pharmacokinetics.

➢ If two drugs have the same elimination rate constant (k) but different absorption rate

constants (ka), which one will reach tmax first? Explain.

➢ At tmax (the peak plasma concentration), drug absorption and elimination occur at the

same rate. How does this impact therapeutic drug monitoring?

➢ Why do some extended-release formulations mimic zero-order absorption, whereas

immediate-release drugs follow first-order absorption?

➢ A drug is given orally and intravenously at the same dose, but its oral bioavailability is

only 30%. What physiological processes are responsible for this loss?

➢ A drug follows first-order absorption with ka = 0.5 hr−1and k = 0.2 hr−1. Calculate tmax

for this drug.

(area under the curve) for IV is 500 mg·hr/L, while for oral it is 300 mg·hr/L. Calculate

its absolute bioavailability (F).

➢ What is the key difference between the Wagner–Nelson and Loo–Riegelman methods

for determining absorption rate constants?

➢ If a drug has a bioavailability (F) of 40%, what oral dose would be required to match the

effects of an IV dose of 150 mg?

➢ A 300 mg oral dose of a drug follows first-order absorption and elimination. Given ka =

0.5 hr−1, k = 0.2 hr−1, and VD= 20 L, determine the plasma concentration (Cp) at 4

hours.

➢ Given plasma concentration-time data for a drug administered orally, how can the

Wagner–Nelson method be used to estimate ka?

Chapter 4: Kinetics following multiple dosing

Questions:

➢ Why is a single dose of a drug usually insufficient for prolonged therapy, and how does

multiple dosing address this limitation?

➢ In a multiple-dosing regimen, what factors determine the optimal dose size and dosing

interval? How do they influence drug accumulation?

➢ What happens if the dosing interval is too short relative to the drug’s elimination half-

life? What risks does this pose?

doses? Why is this useful in clinical settings?

➢ Why does drug concentration reach a steady-state plateau after multiple dosing? What

factors influence the time to reach steady state?

➢ In certain clinical situation, a constant IV infusion be preferred over repeated multiple

dosing. Justify the statement

➢ How does multiple dosing help maintain drug concentration within the therapeutic

window (between MEC and MTC)?

➢ Why is the drug accumulation index (R) independent of dose but dependent on the

elimination rate constant (k) and dosing interval?

➢ Why is a loading dose sometimes necessary in multiple-dose regimens, and how does it

differ from a maintenance dose?

➢ A patient is prescribed an antibiotic that requires a multiple-dose regimen. What factors

should be considered when determining the dose size and frequency to ensure efficacy

and prevent resistance?

➢ A patient on long-term therapy for epilepsy starts experiencing drug toxicity

symptoms. What pharmacokinetic factors could have led to this, and how should the

dosing regimen be adjusted?

➢ A patient forgets to take their regular medication dose. How will this affect their

plasma drug concentration? Should they double the next dose to compensate?

➢ A drug has an elimination rate constant (k) of 0.15 hr−1 and is administered every 8

hours. Calculate the accumulation index (R).

bioavailability (F) of 1. Calculate the steady-state plasma concentration CSS.

➢ A patient needs to achieve a target plasma concentration of 20 µg/mL for a drug with

VD = 50 L. What should the loading dose be?

➢ If a drug has a half-life of 5 hours, how long will it take to reach 90% of steady-state

concentration after multiple dosing?

➢ Two patients receive the same drug dose, but one takes it every 6 hours and the other

every 12 hours. Compare their accumulation index and steady-state levels.

Chapter 6: Bioanalytical Method Validation

Questions

➢ Why is bioanalytical method validation essential in pharmacokinetic, bioavailability,

and bioequivalence studies?

➢ A new antiviral drug is being developed. What factors should be considered in choosing

the most appropriate bioanalytical method for measuring its concentration in plasma?

➢ What is the difference between full validation, partial validation, and cross-

validation? In what situations would each be necessary?

➢ Why is selectivity a crucial parameter in bioanalytical method validation? How can we

ensure that an analyte is detected accurately in the presence of other components?

➢ The Lower Limit of Quantification (LLOQ) defines the lowest measurable drug

concentration in a sample. Why is it important to differentiate LLOQ from Limit of

Detection (LOD)?
➢ In a bioanalytical experiment, two extraction techniques yield different recovery rates.

How does recovery variability affect data reliability?

➢ A method consistently produces nearly identical results, but they differ from the true

concentration of the analyte. Is the method precise, accurate, or neither?

➢ Why must the stability of a drug be tested under freeze/thaw cycles, ambient

temperature conditions, and prolonged storage?

➢ What are the key elements that must be included in bioanalytical method

documentation to ensure regulatory compliance?

➢ A researcher needs to measure low concentrations of a metabolite in plasma. Would

Liquid Chromatography-Mass Spectrometry (LC-MS) or High-Performance Liquid

Chromatography (HPLC) be a better choice? Why?

➢ A company is developing a herbal extract with multiple active compounds. What

validation challenges might arise when developing a bioanalytical method for such a

complex mixture?