Pharmacokinetic Charts

–Ι
21.4.2021
9.5.2022
 Disciplines of Pharmacology Practical
• Be punctual
• Bring your Practical observation note book and get signature of concerned
faculty on the day of practical without fail.
• Bring your practical record note book
• Maintain discipline and silence
• Write the Practical record in home or hostel and get signature of
concerned faculty on next practical day without fail.
• Bring text book, as per instruction
CASE 1
As a clinician, you are concerned with the amount of a drug dose that reaches the
systemic circulation, since this will affect the plasma concentration and therapeutic
effects observed.
1. The pharmacokinetic parameter that will provide you with this information is
given by the drug’s __________ .

A. Theoretical Dose
B. Ideal Dose
C. Cmax
D. Bio-availability
CASE 1
As a clinician, you are concerned with the amount of a drug dose that reaches the
systemic circulation, since this will affect the plasma concentration and therapeutic
effects observed.
2. The parameter in the below chart that will provide you with this information is
given by the drug’s __________ .

A. Target Plasma concentration

B. Cmax
C. AUC
D. Tmax
1. Plasma concentration versus time curve
As a clinician, you are concerned with the amount of a drug dose that reaches the systemic circulation,
since this will affect the plasma concentration and therapeutic effects observed.
1. The pharmacokinetic parameter that will provide you with this information is given by the drug’s
__________ .
2. The parameter in the below chart that will provide you with this information is _____ .
1. Plasma concentration versus time curve
1. Define Pharmacokinetics
2. What is plasma concentration time curve
3. What is absorption and Mention 2 factors affecting it.
4. Define Bioavailability and Mention 2 factors affecting it.
5. Explain briefly the pharmacological parameter used to determine
bioavailability from a plasma concentration-time curve.
 1. Plasma concentration versus time curve
1. What is Pharmacokinetics.
Ans:
Pharmacokinetics is quantitative study of drug movement through the body.
It involves 4 components, namely
Absorption, Distribution, Metabolism and Excretion.
 1. Plasma concentration versus time curve
2. What is a plasma concentration – time curve?
Ans:
After administration of a drug dose to a subject,
plasma samples are obtained at various time intervals and
the drug concentration in the plasma is measured until
the drug is completely eliminated.

These values are plotted on a graph with

time on X-axis and plasma concentration of drug on Y- axis.

It shows the variation of plasma concentration with time.

 1. Plasma concentration versus time curve
3a. What is absorption of a drug ?
Ans:
Absorption of drug is movement of the drug from its
site of administration into the circulation.

In this chart, as the drug is absorbed the plasma

concentration increases and is depicted by the
upstroke of the plasma concentration time curve.

3b. Mention 2 factors that affect absorption of drug.

Ans: Aqueous solubility, Concentration of drug solution,
Area of absorbing surface, Vascularity of the absorbing
surface, Route of administration.
 1. Plasma concentration versus time curve
4a. Define bioavailability
The Rate at which and extent to which the drug reaches the desired site of action or systemic circulation
from its site of administration in its biologically active form.

4b. Mention two factors affecting bioavailability

Fraction absorbed (f) – particle size, solubility, pKa of drug etc.
First pass extraction ratio (ER) – Hepatic blood flow, inter-individual variability

5. Briefly explain the pharmacological parameter used to determine

bioavailability from the plasma concentration-time curve.
Ans:
AUC (Area under curve):
• the area covered by the concentration-time curve
• AUC is the most reliable parameter that reflects the Extent of
absorption and is used to determine Bioavailability.
Plasma concentration versus time curve
2. Plasma Concentration-Time Curves of Three Different Formulations
As a clinician, you are reviewing a formulary submission for new sustained release
formulation of a drug which has an improved side effect profile. However there is
conflicting evidence. So you request to see the results of an Bio-equivalence study.
Out of the three formulations A, B and C, of the same dose of a drug in the below chart
which formulation will you prefer ?
2. Plasma Concentration-Time Curves of
Three Different Formulations
1. What is meant by formulation of a drug?

2. Out of the three formulations A, B and C, of the same drug which formulation
will be preferred? Why?

3. Define Bio-equivalence.

4. What are the pharmacokinetic parameters used to determine Bio-equivalence ?

 2. Plasma Concentration-Time Curves of
Three Different Formulations
1. What is meant by formulation of a drug?
• The final dosage form in which the drug is administered to the patient.

2. Out of the three formulations A, B and C, of the same drug which formulation will be
preferred? Why?
• Formulation A will be preferred because the plasma concentration of only formulation A
reaches the required therapeutic concentration level for the given drug
2. Plasma Concentration-Time Curves of Three Different Formulations
3. Define bioequivalence
‘Two pharmaceutically equivalent drug products are considered to be bioequivalent when
the rates and extents of bioavailability of the active ingredient in the two products are not
significantly different under suitable test conditions.’

4. Mention and briefly explain the pharmacological parameters used to determine

bioequivalence
Rate of Absorption:
Cmax: the peak concentration of a drug that is achieved in plasma
Tmax: the time required to achieve Cmax
Extent of Absorption:
AUC (Area under curve): the area covered by the concentration-time curve
Bio-Equivalence
Gliclazide: 2 different brands Metformin: 2 different formulations
of same dose of a drug of Equivalent dose of same drug
Non Bio-Equivalence
Bupropion 300 mg Bupropion 150 mg
2 different brands: Wellbutrin XL vs Budeprion XL 2 different brands: Wellbutrin XL vs Budeprion XL
3. Food and Drug influencing Absorption of
Another Drug
 3. Food and Drug influencing Absorption of
Another Drug
1. What is the effect of coadministration of antacid or milk on
tetracyclines?

2. What is the mechanism behind this effect?

3. Which other substances can produce similar effect on

absorption of tetracyclines?

4. Which tetracyclines are free from such an effect?

5. Mention some other drugs where presence of food affects

absorption
3. Food and Drug influencing Absorption of
Another Drug
1. What is the effect of coadministration of antacid or milk on
tetracyclines?
• Absorption of tetracyclines is reduced in the presence of antacids or
milk
2. What is the mechanism behind this effect?
• Tetracyclines have chelating property: they form insoluble and
unabsorbable complexes with calcium and other metals.
3. Which other substances can produce similar effect on absorption of
tetracyclines?
• Iron preparations and sucralfate also reduce tetracycline absorption
 3. Food and Drug influencing Absorption of
Another Drug
4. Which tetracyclines are free from such an effect?
• Doxycycline and minocycline are completely absorbed irrespective of
milk
5. Mention some other drugs where presence of food affects absorption
• Better absorbed in acidic medium: Amprenavir, itraconazole and
ketoconazole
• Presence of bile acids or fat enhances absorption: carbamazepine,
griseofulvin, halofantrine, mefloquine, acitretin, isotretinoin, saquinavir,
and tacrolimus
 4. Blood-Brain Barrier
A 35 year old male working as a driver is prescribed diphenhydramine (anti-histamine)
for his allergy symptoms post an insect bite. The patient returns the next day
complaining of excessive drowsiness that is interfering with his work.

1. How is this drug able to cause sedation (CNS effect) by crossing the BBB? Choose the most likely
explanation.
a) It is a weakly acidic drug
b) It is a hydrophilic drug
c) It is ionized at physiological pH (7.4)
d) It is lipophilic and non-ionized at physiological pH (7.4)
4. Blood-Brain Barrier
1. Why is a blood-brain barrier needed?
2. What is BBB composed of ?
3. What are the conditions where in there are physiological and pathological
deficiencies in BBB ?
4. Give one therapeutic application with example.
5. Name other similar barriers for drug transport in the body
 4. Blood-Brain Barrier
1. Why is a blood-brain barrier needed?
• To protect the structures of brain from potentially harmful effects of drugs and exogenous chemicals
2. What is BBB composed of?
• Anatomical: Tight junctions, Neuro-glial cells, choroidal epithelium
• Physiological: Specialized Efflux pumps Eg: P-glycoprotein, OATP etc
• Enzymatic: Neurotransmitter and drug metabolizing enzymes such as cholinesterases, GABA transaminase,
aminopeptidases and endopeptidases.
3. Which regions or under what conditions can drugs act in CNS?
Drugs can act at regions of physiological deficiencies or during pathological inflammation of BBB.
• Physiological: circumventricular organs: Pineal gland, Subfornicial organ, Median eminence, OVLT (organum
vasculosum of lamina terminalis), Area Postrema, Posterior pituitary
• Pathological states: Meningitis, brain abscess, Alzheimer's disease, multiple sclerosis, cerebral edema, etc.
4. Blood-Brain Barrier
4. Give one therapeutic application with example.
• Dopamine cannot cross BBB, but levodopa can cross.
• Therefore, in the treatment of parkinsonism, even though the active drug is
dopamine, it is given in the form of levodopa so that the active drug be delivered
into the brain.

5. Name other similar barriers for drug transport in the body

• Blood-CSF barrier, placental barrier
5. Biotransformation
Phase 1 drug metabolism differs from phase 2 in that
1. Phase 1 metabolism always occurs prior to phase 2
2. Phase 1 occurs in intestine but phase 2 occurs in liver
3. Phase 1 occurs during 1st pass metabolism but phase 2 occurs later
4. Phase 1 activates prodrug but phase 2 inactivates the prodrug
5. Phase 1 functionalize drugs but phase 2 conjugates drug
5. Biotransformation
1. Define biotransformation

2. Which is the primary site for drug biotransformation in the body? Name the
other organs where biotransformation is seen.

3. What are the phases in biotransformation?

4. What is meant by first pass metabolism?

5. What is a prodrug? Give some examples

 5. Biotransformation
1. Define biotransformation
• It is the process by which exogenous drugs and chemicals are converted into lipid-
insoluble forms so as to facilitate their excretion from the body

2. Which is the primary site for drug biotransformation in the body? Name the other
organs where biotransformation is seen.
• Liver is the primary site for biotransformation.
• Other organs are skin, intestines, lungs, kidney, plasma

3. What are the phases in biotransformation?

• Phase l/ non-synthetic/ functionalization reactions
• Phase II/ synthetic/ conjugation reactions
 5. Biotransformation
4. What is meant by first pass metabolism?
• Also known as pre-systemic metabolism. This is the metabolism of drugs before they
can enter into systemic circulation. Predominantly occurs in the liver; predominantly
seen with orally administered drugs

5. What is a prodrug? Give some examples

• A prodrug is a biologically inactive precursor of an active drug.
• Prodrugs get converted into their active forms following biotransformation.
• Examples:
• levodopa  dopamine;
• Enalapril  enalaprilat;
• Dipivefrine  epinephrine
6. Half-life
6. Half-life

1. What is plasma half-life (t ½)?

2. What is the α slope due to?

3. What is the β slope due to?

4. Name 2 drugs with long t ½ and 2 drugs with short t ½

5. Enumerate the factors affecting t ½ and how to calculate t ½

 6. Half-life
1. What is plasma half-life (t ½)?
• Time required for a 50% reduction in the plasma concentration of the drug from its
initial concentration
2. What is the α slope due to?
• α is due to rapid distribution of the drug within the body into the tissues
3. What is the β slope due to?
• β is due to slow elimination of the drug
4. Name 2 drugs with long t ½ and 2 drugs with short t ½
• Long half life: Digitoxin, Procaine penicillin, Alendronate
• Short half life: Adenosine, esmolol, levodopa, insulin
5. Enumerate the factors affecting t ½
• Volume of distribution and clearance
7. Kinetics of Elimination
1. Which of the following accurately describes
the relationship between 1st order kinetics and
drug elimination?
A. The elimination half-life is proportional to the

plasma drug concentration

B. The drug is eliminated at a constant rate
C. The rate of drug elimination is proportional to
plasma drug concentration
D. The hepatic P450 enzymes become
saturated
 7. Kinetics of Elimination
1. Define first order elimination kinetics

2. Define zero order elimination kinetics

3. Name some drugs eliminated by zero order kinetics and pseudo zero
order kinetics

4. What is the clinical importance of zero order kinetics?

5. What is the mechanism of occurrence of zero order kinetics?

7. Kinetics of Elimination
1. Define first order elimination kinetics
• First order kinetics is when the rate of elimination is directly proportional to the
concentration of the drug:
• as the concentration of drug in plasma increases, the rate of elimination also
increases.
• Meaning, a constant fraction of the drug is eliminated in unit time

2. Define zero order elimination kinetics

• Zero order kinetics is when the rate of elimination remains constant irrespective
of the drug concentration.
• Meaning, a constant amount of the drug is eliminated in unit time, irrespective of
how much drug is present in the plasma.
7. Kinetics of Elimination
3. Name some drugs eliminated by zero order kinetics and pseudo zero order
kinetics
• Zero order: ethanol
• Pseudo zero order: Phenytoin, warfarin, theophylline, Tolbutamide
4. What is the clinical importance of zero order kinetics?
• Drugs having zero order kinetics tend to accumulate in the body during toxicities.
Therefore while increasing doses of these drugs one must be extremely careful
5. What is the mechanism of occurrence of zero order kinetics?
• Zero order kinetics occurs because of saturation of the metabolizing enzymes
Thank you