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CHAPTER 2
DEFINITIONS RELATED TO
PHARMACOKINETICS
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PHARMACY
The Pharmacist has to learn:
 What physiological factors affect drug
release
 To calculate fraction of the dose of drug
absorbed
 To learn PK to calculate the rate of
absorption
 Patients counseling and physicians
advising about drug products and their use
(clinical pharmacist)
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PHAMACOKINETICS (PK)
The WHO defines PK as:
“The study of the absorption, distribution,
metabolism, and excretion of drugs”.
This definition lacks:
“The concept that you have to apply
mathematics and modeling to data collected in
studies of absorption, distribution and
elimination of drugs before PK is involved”.
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PURPOSE of PK
In PK the data are processed using a
mathematical representation of a part
or the whole of an organism
 To reduce data to meaningful
numbers of parameters
 To use the reduced data to make
predictions of results of future
experiments
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How We Study PK of Drugs?
The study involves and Experimental
and a Theoretical approach.
Experimental part consists of:
Biological sampling techniques,
analytical methods, data collection and
manipulation.
Theoretical part consists of:
Development of PK models that predict
drug disposition after administration.
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CLINICAL PK
“The application of PK to the safe and
effective therapeutic management of the
individual patient”. Its functions include:
Design of drug dosage regimens
 Readjustment of dosage regimens when
 necessary
 Investigate the reason behind an unusual
 response
 Educational activities directed to physicians,
pharmacists, nurses, and patients.
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PHARMACODYNAMICS (PD)
Refers to the relationship between the drug
concentration at the site of action (receptor)
and pharmacologic or toxic response.
PK-PD Models
are constructed to relate the plasma drug
level to the concentration of the drug in the
site of action and establish the intensity and
time course of the drug.
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BIOPHARMACEUTICS
Considers the interrelationship of the physicochemical properties of the drug, the dosage
form, and the route of administration on the rate
and extent of systemic drug absorption
Biopharmaceutics Methods
Must be able to assess the impact of the
physico-chemical properties of the drug, drug
stability, and large scale production of the drug
and drug product on the biological performance
of the drug
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Dynamic Relationship
Drug release
and
dissolution
Absorption
Drug in Systemic
circulation
Elimination
BIOPHARMACEUTICS
Excretion and
metabolism
Drug in tissues
PK
PD
Pharmacologic or
clinical response
Relationship between the drug, the drug
product and the pharmacologic effect
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BIOAVAILABILITY (F)
“is defined as the fraction of the administered
dose reaching the systemic circulation of the
patient”.
Factors Affecting BA:
Inherent
dissolution
and
absorption
characteristics of the administered chemical
form (salt, ester), the dosage form (tablet,
solution,..), the route of administration, the
stability of the drug in the GI tract, and the
extent of drug metabolism.
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First-Pass Effect
Refers to the loss of drug as it passes for the
first time through organs of elimination such as
the GI membrane and liver during the drug
absorption process.
Portal
Circulation
Gut
Wall
Gut
Lumen
L
i
v
e
r
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Intravascular administration
• All rout of administration where the drug is
directly introduced in to blood stream.
Intravenous, intra arterial. And intra
cardial.
• Extra vascular, All rout of administration,
Im, Sc, oral, rectal, topical, trans dermal
,etc.
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Plasma level time curve
• Is generated by obtaining the drug
concentration in plasma samples taken at
various time intervals after a drug product
is administered.
• The concentration of drug in each plasma
sample is plotted on rectangular
coordinate graph paper against the
corresponding time at which the plasma
sample was removed
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Blood flow rate
• The speed of blood perfusion in an organ,
usually expressed in ml/100gm organ
weight. Blood flow rates may differ
several-folds between rest and exercise.
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Definitions you should know
• Pharmacokinetics, intravascular,extravascular
• Absorption (process by which a drug proceeds from
the site of administration to the site of measurement
within the body.
• Disposition(all the processes that occur subsequent
to the absorption of a drug
• Distribution ; reversible transfer of a drug to and
from the site of measurement.
• Metabolism; irreversible conversion to another
chemical species.
• Excretion; irreversible loss of the chemically
unchanged drug
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• Accumulation; the increase of drug concentration in blood and tissue
upon multiple dosing until steady state is reached
• Steady state; the level of drug accumulation in blood and tissue
upon multiple dosing when input and output are at equilibrium .
• Biophase;the actual site of action of drug in the body.
• A receptor; a site in the biophase to which drug molecules can be
bound
• A compartment in pharmacokinetics; an entity which can be
described by adefinite volume and concentration of drug contained
in that volume. In pharmacokinetics , experimental data are
explained by fitting them to compartmental models.
• Central compartment; the sum of all body regions( organs and
tissue) in which the drug concentration is in instantaneous
equilibrium with that in blood or plasma. The blood or plasma is
always part of the central compartment
• Peripheral compartment; the sum of all body regions to which a drug
is eventually distributes but is not in instantaneous equilibrium.
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• Feathering ; refers to a graphical method for separation of
exponents such as separating the absorption rate constant from the
elimination rate constant. ( residual method)
• Biliary recycling; the phenomenon that drugs emptied via bile in to
the small intestine can be reabsorbed from the intestinal lumen in to
systemic circulation.
• Apparent partition coefficient; the ratio of the concentration at
equilibrium between a lipoid phase (n, octane) and an aqueous
phase ( buffer ph 7.4).
• Area under the curve; the integral of drug level over time from zero
to infinity, and Isa measure of the quantity of drug absorbed in the
body.
• Clearance rate; the volume of blood in ml which is completely
cleared of the drug per unit time (minute) by urinary excretion or
metabolism.
• Renal clearance; the hypothetical plasma volume (volume of plasma
volume (volume of of unmetabolized drug which is cleared in one
minute via the kidney.
• Hepatic clearance; the hypothetical plasma volume (volume of
distribution) in ml of the metabolized drug which is cleared in one
minute via the liver
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Significance of measuring plasma drug
concentration
• Checking the plasma drug level is a responsive method of
monitoring the course of therapy
• Monitoring the concentration of drugs in blood or plasma ascertain
that the calculated dose actually deliver drug required for
therapeutic effect.
plasma
• Is needed to distinguish
thevolume
patient(volume
who isof
receiving too much drug
from the patient who is supersensitive to the drug.
• Allows for the adjustment of the drug dosage in order to individualize
and optimize therapeutic drug regimens.
• Provide a guide to the progress of the diseased state and enable the
investigator to modify the drug dosage accordingly(in clinical
pharmacokinetics).
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