Pharmacy and Biotechnology
Department of Pharmaceutical Technology 1
Biopharmaceutics &
Pharmacokinetics
[PHTC 523]
LECTURE 1: “INTRODUCTION TO BIOPHARMACEUTICS
AND PHARMACOKINETICS”
COURSE INSTRUCTORS:
DR. SHAHIR AZIZ
DR. SALMA TAMMAM
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Course Outline 2
1) Introduction to Pharmacokinetics 7) The Intravenous Route (4):
2) Bioavailability & Bioequivalence (1): 8) The Oral Route (1):
3) Bioavailability & Bioequivalence (2): 9) The Oral Route (2):
4) The Intravenous Route (1):
10) Multiple dosing:
11) Pharmacokinetic Parameters Determination from
5) The Intravenous Route (2):
Urine Samples
6) The Intravenous Route (3): 12) Non-Compartmental Pharmacokinetics
Course Assessment 3
Student assessment methods Assessment weighting
Assigned activity 10%
Quizzes (2/3) 20%
Midterm Exam 30%
Final Exam 40%
Course References
1) Applied Biopharmaceutics & Pharmacokinetics, 5th edn. by Leon Shargel
2) Basic Clinical Pharmacokinetics, 4th edn. by Michael E. Winter
3) Modern Pharmaceutics. 4th edn., by G. S. Banker
Course ILOs 4
1. Define and Use the proper pharmaceutical terms and symbols in pharmacokinetics and
biopharmaceutics practice.
2. Recognize the different factors affecting drug Absorption, Distribution and Metabolism.
3. Identify the dosing types, regimens and how such factors will affect the pharmacokinetic, and
bioavailability parameters. In addition to the physiological factors that affect the drug bioavailability.
4. Identify how disease may alter normal pharmacokinetics and hence the need of tailored dosing
regimens.
5. Identify how genetics may alter normal pharmacokinetics( pharmacogenetics) and hence the need of
tailored dosing regimens.
6. Evaluate the effect of different physiological factors on the drug bioavailability when formulating a new
medicine to guarantee safety and effectiveness.
7. Demonstrate critical thinking, problem- solving & decision-making abilities related to assignment and
tutorial discussions.
Lecture 1 - Outline 5
Biopharmaceutics Basic Principles:
Definitions
Routesof drug administration
Measurement of drug concentrations
Measurement Parameters
Guidance for pharmaceutical Industry
Guidance for Clinical practices
Oral Target
6
Tissue /
Medication Organ Stomach
Parenteral
Medication
Hepatic circulation
Small
intestine
Heart
Liver
Liberation
Absorption
Distribution
Metabolism Large
intestine
Excretion Distribution by Blood Circulation
Toxicity
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Basic Principles
7
Definitions
Biopharmaceutics:
The study of the interrelationship between the drug formulation and the therapeutic effect of
the drug (or the bioavailability of the drug)
Pharmacodynamics (PD):
The study of the interrelationship between the drug concentration at the site of action and its
pharmacological and therapeutic effect.
Pharmacokinetics (PK):
The study of the drug Kinetics (movement) through the body by; ADME or L-ADME or ADME-T
Clinical Pharmacokinetics: is the application of the pharmacokinetics data/methods to the
most effective and safe therapeutic management (dosing) of an individual patient.
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Basic Principles
8
Definitions
PD Profile: PK Profile:
Effect Concentration
Concentration Time
PK: The time course of the drug and metabolite concentrations in the body.
PD: The pharmacological effect for varying concentrations in the body
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Basic Principles
9
Routes of drug Administration
Parenteral: from outside the intestine, indicating IV, IM, SC, inhalation, topical ..etc.
Enteral: Through the oral cavity and into the GIT
Parenteral
Enteral
Injections Topical
Intravenous (IV), Intramuscular
Inhaled (lungs), nasal, vaginal,
Oral, Sublingual, Rectal (IM), subcutaneous (SC), Intra-
ophthalmic
arterial, …etc.
Intravascular administration: drug introduced directly into the blood stream (i.e.: IV, Intra-
arterial and Intra-cardial)
Extravascular administration: drug went through absorption process to reach the blood
indirectly (i.e.: all other administration routes)
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Basic Principles
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Measurement of drug concentration
Concentration in Blood, plasma or serum:
Most direct approach to assess pharmacokinetics of the drug in the body
Concentration in Tissues:
Tissues biopsies for diagnostic purposes mainly and very difficult to assess pharmacokinetics
Concentrations in Urine and feces:
Indirect method, by assessing the rate and extent of drug excreted reflecting the rate and
extent of drug absorbed.
Concentrations in Saliva:
Secondary indicator after plasma drug concentrations, that help in assessing the
pharmacokinetics of certain type of drugs
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Basic Principles
11
Measurement Parameters
Typical single dose Plasma concentration drug profile
Maximum Therapeutic
concentration
Maximum Plasma
Concentration
Elimination Phase
Minimum Effective
concentration
Absorption Phase
Area Under
the Curve
Oral or IV?
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Basic Principles
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Measurement Parameters
Typical Oral single dose (Left) and multiple dose (right) Plasma
concentration drug profiles
The therapeutic range is that
range of serum drug
concentrations which have
been shown to be effective
without causing toxicity in the
majority of patients.
Therapeutic drug monitoring (TDM) is the measurement of the serum level of a drug and
the coordination of this serum level with a therapeutic range.
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Basic Principles
13
Measurement Parameters
LADME processes can be divided into two classes;
Drug Input and Drug Output.
D = Distribution, the process by which drug diffuses
or is transferred from intravascular space to
L = Liberation, the release of the drug from it's extravascular space (body tissues).
dosage form.
M = Metabolism, the chemical conversion or
transformation of drugs into compounds which are
A = Absorption, the movement of drug from easier to eliminate.
the site of administration to the blood
circulation. E = Excretion, the elimination of unchanged drug or
metabolite from the body via renal, biliary, or
pulmonary processes.
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Basic Principles
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Bioavailability
The percentage or fraction of the drug of the administered dose
reaching the systemic circulation. It indicates the rate and extent of
drug absorbed and become available for the pharmacological
effect.
Intravenous administration is considered to yield 100% absorption which gives a absolute
bioavailability factor of [1]. In comparison, any other extravascular administration route will
always yield a relative bioavailability factor of [< 1].
E.g.: The bioavailability of “Digoxin” from orally administered tablets is estimated to be [0.7]. If
admitted dose per tablet is (0.25 mg),
Then the amount of drug absorbed = (0.7 x 0.25mg = 0.175 mg = 175µg)
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Basic Principles
15
Administration Rate
The average rate at which absorbed drug reaches the circulation. Usually calculated
by dividing the amount of drug absorbed over the time interval of the absorption
process or by the dosing interval.
E.g.: The average administration interval for Digoxin tablets is one per day
So the administration rate is 175µg / day
= 175µg / 24hr. = 7.29 µg/hr.
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Basic Principles
16
Distribution
Drug's volume of distribution; is that volume of body fluid into which a drug dose is dissolved
Volume of distribution = Dose / drug concentration
Central volume (Vc): Peripheral (tissue) volume (Vt)
Is a hypothetical volume into which a Is the sum of all tissue spaces outside the
drug initially distributes upon central compartment. Of course, all
administration. This compartment can peripheral tissues are not homogenous,
be thought of as the blood in vessels this is a simplification for the purpose of
and tissues (e.g.; Kidney & Liver) which creating a usable mathematical model.
are highly perfused by blood.
N-
1 compartment
compartments
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Basic Principles
17
Elimination
Clearance (CL) Urine
analysis
Is a descriptive term used to evaluate efficiency of
drug removal from the body.
Clearance is not an indicator of how much drug is
being removed; it only represents the theoretical
volume of blood which is totally cleared of drug per
unit time.
Units = Volume/Time
Plasma
analysis Schematic Diagram representing drug clearance through the kidneys
https://pharmafactz.com/basic-principles-of-drug-clearance/
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Case Study
18
Plasma concentration time Profile of
three patients (A, B & C) after the
administration of the same mg dose
of the same drug “X”.
The figure represents which of the
following; Pharmacokinetics or
Pharmacodynamics?
Pharmacokinetics IV
What are the possible routes of Oral
administration for each?
Between subjects A & B, when is
Drug X eliminated faster?
A has Steeper curve = Faster Elimination
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
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Why
Biopharmaceutics and
Pharmacokinetics?
Guidance for Guidance for
Industry Clinical practices
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
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Bioavailability &
Bioequivalence
Guidance for Industry
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Bioavailability & Bioequivalence
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Guidance for industry
Which to use?
All are 500 mg dose
Acetaminophen
/tablet but different
brand names
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Bioavailability & Bioequivalence
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Guidance for industry
Which to use?
All are 500 mg dose
Acetaminophen
/tablet but different
brand names
Average Paracetamol concentration vs. time in a
pharmacokinetic study of18 healthy male volunteers
under fasting conditions
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Bioavailability & Bioequivalence
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Guidance for industry
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Bioavailability & Bioequivalence
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Guidance for industry
Bioavailability is defined as: the Rate and Extent … (Slide 12)
Bioequivalence is defined as: the absence of a significant difference
in the Rate and Extent to which the active ingredient in pharmaceutical
alternatives becomes available at the site of drug action when
administered at the same molar dose under similar conditions in an
appropriately designed study.
The purpose of bioequivalence studies is to demonstrate bioequivalence
between a pharmaceutically equivalent generic (Test) drug product, and the
corresponding reference listed drug (Original brand name) .
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
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Bioavailability &
Bioequivalence
Guidance for Clinical
practices
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
Bioavailability & Bioequivalence
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Guidance for Clinical practices
According to the Swiss association of public health administration and
Hospital Pharmacists (GSASA);
• Clinical pharmacy is aimed at developing and promoting an
appropriate, safe and cost-effective use of therapeutic products.
• In the hospital setting, clinical pharmacy includes direct patient
oriented pharmaceutical activities, implemented in collaboration
with other health care professionals.
• Clinical pharmacists have a dedicated training program in this field
and assume the responsibility of their interventions.
Dr. Shahir Aziz – (PHTC 523) – Winter 2022
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Thank you
