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PHT 415
BASIC PHARMACOKINETICS
Course Instructor:Prf. Dr. Hnaa elsaghir
Assistant lecturers, Doaa elshora and eman elfakih
Text: Hand book of basic pharmacokinetics, and lab
notes.
Grading: Quizes (5 pts), Midterm (10 pts), Final (20
pts),), Practical (10 pts) for attendance 5 pts
Lectures: sunday 11-12, Wednesday 11-12 (
Office Hours: Sunday and Wednesday 8 -10
Email: [email protected]
PK and PD
PK is the study of what the body does to a drug
PD is the study of what a drug does to the body
DRUG THERAPY
Duration of Drug Therapy:
Single Dose:
such as to relieve a headache
For the Rest of the Patient’s Life:
such as in chronic diseases (epilepsy,
diabetes)
DOSAGE REGIMEN
The manner in which a drug is taken is
called a Dosage Regimen
Duration of Drug Therapy and Dosage
regimen will depend on the therapeutic
objective.
Objectives of taking a drug are :
Cure, Mitigation, Prevention
SUCCESSFUL DRUG THERAPY
By optimally balancing the desirable and
undesirable effects
 Accurate diagnosis is made
 Drug of choice
 Knowledge of clinical state of patient
 Understanding the pharmaco-therapeutic
management of the disease
 Answer the questions How much? How
often? and How long?
Answers to Questions??????
How much? Recognizes that the magnitude of
the therapeutic and toxic responses is a
function of the dose given.
How often? Recognizes the importance of
time, in that the magnitude of the effect
eventually declines with time following a single
dose of drug.
How long? Recognizes that a cost (in terms of
side effects, toxicity, economics) is incurred
with continuous drug administration.
In the Past
Questions were answered by trial and error,
i.e. the dose, interval between doses, and route
of administration were selected and the
patient’s progress was followed. This empirical
approach established many dosage regimens
but left many questions unanswered!!!!!!
This empirical approach did not contribute
toward establishing a safe, effective dosage
regimen of another drug, i.e. did not help us
understand how drugs work?
Event that follows drug administration
Plasm a Theophylline Concentration (m g/L)
6
5
4
3
2
1
0
0
12
24
36
48
Hours
Plasma conc of theophylline after an oral dose of 600-mg
Application of Pharmacokinetics
Rarely is a drug placed at its site of action,
most drugs are given orally and yet they act in
the brain, heart, or elsewhere!!!!
Which means a drug has to move from the site
of administration to the site of action.
Therefore to administer drugs optimally,
knowledge is needed not only of the
mechanisms of drug absorption, distribution,
and elimination but also the kinetics of these
processes, that is PK
Following Drug Administration 2
phases can be distinguished
Pharmacokinetic Phase: in which the
adjustable elements of dose, dosage form,
frequency, and route of administration are
related to drug level-time relationships in the
body.
Pharmacodynamic Phase: in which the
conc of drug at the site of action(s) is related
to the magnitude of the effect(s) produced.
Aimes of PK and PD
Knowing the PK and PD of drugs will aid
in designing a dosage regimen to achieve
the therapeutic objective.
OPTIMIZE PATIENT
DRUG THERAPY BY
MONITORING PK&PD
RESPONSES
Advantages over the Empirical
Approach
1- Distinction can be made between PK and
PD causes of an unusual drug response.
2- Information gained about the PK of one drug
can help in anticipating the PK of another drug.
3- Understanding the PK of a drug often
explains the manner of its use.
4- Knowing the PK of a drug aids the clinician
in determining the optimal dosage regimen for
a patient and in predicting what may happen
when a dosage regimen is changed.
An Approach to the Design of a Dosage
Regimen
Pharmacokinetics
Dosage
Regimen
Pharmacodynamics
Plasma
Concentration
Site
of
Action
Effects
Where to Measure Concentration?
Rarely can the concentration of the
drug at the site of action be
measured directly; instead the
concentration is measured at an
alternative and more accessible
site, the plasma.
What is then an optimal
dosage regimen?
It is the one that maintains
the plasma concentration of a
drug within the therapeutic
window and then maintaining
this concentration by
replacing the amount of drug
lost with time.
Initial and Maintenance Dose
Two different regimens A and B, B=2A
Plasma conc
Regimen B
Therapeutic
Window
Regimen A
Time
Therapeutic Window (TW)
 The size and frequency of the maintenance
dose depends on the width of the therapeutic
window and the speed of drug elimination.
 When the window is narrow and the drug is
eliminated rapidly, small doses must be given
often to achieve therapeutic success.
 Both cyclosporine and digoxin have a narrow
TW, but because cyclosporine is eliminated
much more rapidly than digoxin, it has to be
given…?…?…?…?…? ( more frequently or
less frequently)
Oxytocin
 Oxytocin is an extreme example, it also has
a narrow TW, but it is eliminated within
minutes. The only means to ensure a
therapeutic conc is to infuse it at a precise and
constant rate directly into the blood (i.v.
infusion). Oxytocin can not be given orally
because it is destroyed in the GIT.
 Morphine can not also be given orally
because it is extensively metabolized in the
liver.
PROBLEM!!!
Variability in Clinical Response
 Sources of variability: patient’s age,
weight, degree of obesity, type and severity of
disease, the patient’s genetic makeup, others
drugs concurrently administered and
environmental factors.
 Result: A standard dosage regimen of a
drug may prove therapeutic in some patients,
ineffective in others and toxic is still others.
Dosage Regimen Adjustment
The need is greatest for drugs with narrow
TW:
 Digoxin used to treat cardiac disorders.
 Phenytoin used to prevent epileptic
convulsions
 Theophylline used to diminish chronic
airway resistance in athmatics.
 Cyclosporine used as immunosuppressant
in organ transplantation.
 Warfarin used as oral anti-coagulant.
Drug-Drug Interaction
Interactions that result in a change in PK of
a drug could be due to:
 Stimulation of drug metabolizing enzymes
therefore increasing drug loss.
 Inhibition of drug metabolizing enzymes
therefore slowing drug elimination and
increasing its concentration in the blood.
 Interference with drug absorption.
SOLUTION
A pragmatic approach to this problem
would be to adjust the dosage until the
desired objective is achieved.
Control on a dosage basis alone,
however, has proved difficult.
Control is achieved more readily and
accurately when plasma drug
concentration data and the PK of the drug
are known.
DRUG IS A VERY COMPLEX SYSTEM
WHAT WE WILL DO IN
THIS CLASS?
 Although the details of drug kinetics are
complicated, it is fortunate that we can often
approximate drug kinetic processes using
“SIMPLE MATHEMATICAL MODELS”.
 The use of PK equations, rather than the
derivation of the equations will be taught in
this class.