INTRODUCTION TO BP-PK &

LADMER SYSTEM
Lecture By : Abdul Mannan
Definition of
Biopharmaceutics

Biopharmaceutics is a major branch of the pharmaceutical
sciences concerned with the relationship between the
physicochemical properties of a drug in dosage form and the
pharmacologic, toxicologic, or clinical response observed
after its administration (Gibaldi, 1991).
or
Biopharmaceutics is the study of the factors influencing the
bioavailability of a drug in man and animals and the use of
this information to optimize pharmacological and therapeutic
activity of drug products

Thus biopharmaceutics deals with the
factors that influence the

protection of the activity of the drug within
the drug product (stability)
the release of the drug from the a drug product
the rate of dissolution of the drug at the
absorption site, and
the systemic absorption of the drug.

Studies of biopharmaceutics involves
both in-vitro and in-vivo methods.

In-vitro methods involves test apparatus
without involving laboratory animals or
humans. E.g. disintegration tests, dissolution
tests etc.
In-vivo test involves measurement of systemic
drug availability (bioavailability) after giving
a drug product to an animal or human
Schematic Representation of
the Process involved in B&P
Drug in dosage form
Drug at absorption site
Drug release
Drug in systemic circulation
Drug absorption
Drug in extravascular tissues
Drug at site of action
In normal body
Pharmacologic response
In diseased body
Therapeutic effect at therapeutic dose
Toxic effect at toxic dose
BIOPHARMA
CEUTICS
PHARMACO
KINETICS
Elimination
Metabolism
Excretion
DISPOSITION
Schematic representation of the process involved in drug therapeutics
PHARMACODYNAMICS
THERAPEUTICS
Pharmacokinetics
Defination
Pharmacokinetics is defined as the study
of rate processes involved in absorption,
distribution, metabolism and excretion (ADME).


Pharmacokinetics
Absorption Disposition
Distribution Elimination
Excretion Metabolism
Overall Pharmacokinetic Parameters
Absorption rate constant ( K
a
)
Extent of bioavailability ( F )
Half life ( t

)
Effective concentration range
Blood plasma concentration ratio
Apparent volume of distribution ( V
d
)
Fraction of protein binding (F
b
)
Peak concentration (C
max
)
Time to reach peak concentration (t
max
)
Toxic concentrations
First order elimination rate constant (K)
Fraction of dose excreted unchanged in urine ( X
u

)
Clearance (Total, Renal, Hepatic, etc.) (Cl)


The study of pharmacokinetics involves both
experimental and theoretical approaches.
The experimental approach involves :
The development of biological sampling
techniques
Analytical methods development for the
measurement of drugs and metabolites
And the procedures for data collection and
manipulation.


The theoretical aspect of pharmacokinetics
involves :

The development of pharmacokinetic models
that predicts drug disposition after drug
administration.
The application of statistics is an integral part
of pharmacokinetic models top determine
data errors, deviation of models and
correlation.

Application of Pharmacokinetics :
Drug Development
Clinical Pharmacy
Deciding Dosage Regimen
Deciding Rational Dose, Frequency And Duration
Formulation Development
Rational Drug Design (QSPKR)
ADME Study, Bioavailability Or Bioequivalence
Studies
In Vitro In Vivo Correlation Studies
Pharmacokinetics Pharmacodynamics Relationship.
Applications of pharmacokinetics:

Effects of physiological and pathological conditions on
drug disposition and absorption
Dosage adjustment of drugs in disease states, if and
when necessary
Correlation of pharmacological responses with
administered doses
Evaluation of drug interactions
Clinical prediction: using pharmacokinetic parameters to
individualize the drug dosing regimen and thus provide
the most effective drug therapy


Role of pharmacokinetics in various stages
of drug development


Stage of development
Selection of drug
candidates for
development

Preclinical
development


Clinical development:
phase 1, 2 & 3.
Role of pharmacokinetic studies
Consideration of the pharmacokinetic
profile desired in connection with
known biotransformation processes;
explorative in vitro studies.
Design and interpretation of
pharmacological and toxicological
investigations also with respect to
species differences.
Establishing dosage regimens,
absolute:relative bioavailability,
identification of metabolites and
evaluation of their contribution to the
biological profile of the drug. Studies in
special patient groups at potential risk
(age, disease, metabolic disorders, co-
medications) to adjust dose regimens.
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Parameters in PHARMACOKINETIC Study
Onset
The time it takes for the drug to elicit a therapeutic
response
Peak
The time it takes for a drug to reach its maximum
therapeutic response
Highest blood level
Trough Level
Lowest blood level
Duration
The time a drug concentration is sufficient to elicit a
therapeutic response
Plasma Drug Concentration :
Measurement of drug concentrations in blood, plasma, or serum after
drug administration is the most direct and objective way to determine
systemic drug bioavailability.

C
max
. The peak plasma drug concentration, C
max
, represents the
maximum plasma drug concentration obtained after oral administration
of drug. For many drugs, a relationship is found between the
pharmacodynamic drug effect and the plasma drug concentration. C
max

provides indications that the drug is sufficiently systemically absorbed
to provide a therapeutic response. In addition, C
max
provides warning
of possibly toxic levels of drug. The units of C
max
are concentration
units (eg, mg/mL, ng/mL). Although not a unit for rate, C
max
is often
used in bioequivalence studies as a surrogate measure for the rate of
drug bioavailability.


15
t
max
. The time of peak plasma concentration, t
max
,
corresponds to the time required to reach maximum drug
concentration after drug administration.
At t
max
, peak drug absorption occurs and the rate of drug
absorption exactly equals the rate of drug elimination. Drug
absorption still continues after t
max
is reached, but at a
slower rate.
When comparing drug products, t
max
can be used as an
approximate indication of drug absorption rate. Units for t
max
are units of time (eg, hours, minutes).
AUC. The area under the plasma leveltime curve, AUC, is a
measurement of the extent of drug bioavailability. The AUC reflects
the total amount of active drug that reaches the systemic circulation.
The AUC is the area under the drug plasma leveltime curve from t =
0 to t = , and is equal to the amount of unchanged drug reaching the
general circulation divided by the clearance.

LADMER SYSTEM
INTRODUCTION TO
LADMER SYSTEM INTRODUCTION
The ultimate aim of a drug is to achieve optimal
therapy.

To attain this aim the drug is first molded into a
suitable dosage form.
The dosage form is administered in to the body
through a suitable route of administration.
The drug is released at the site of absorption at
a certain rate.
The drug is then absorbed from the site of
absorption to systemic circulation.
The drug is carried to various tissues through blood. The
drug is distributed to extravascular tissues. The distribution
method is a reversible process. The drug returns back to
the systemic circulation
The drug produces its action at the site of action. The site
of action may reside in some extravascular tissues.
The drug is excreted through kidney and metabolize in the
liver and various tissues. Thus the drug is eliminated from
the body.
All the above processes are occurring at a certain rate.
Under the subject pharmacokinetics we study those rates
and built up equations to predict those rate processes. And
in the Ladmer system the relationship between the release,
ADME & its response is studied.

Interdisciplinary scheme of LADMER
system
LADMER SYSTEM
LADMER liberation, absorption, distribution,
metabolism, and elimination (are involved to elicit the)
response.
Ladmer system describes the relationship of liberation
of drug from the dosage form with absorption into the
systemic circulation, distribution throughout the body,
metabolism in various systems. And finally excretion
from the body & the response on effect.

The ladmer system provide the basis for achieving the
desired therapeutic drug concentration while avoiding
unnecessary toxicity.
The fate of drugs is described in the biopharmaceutics and
pharmacokinetics by the LADMER system, showing that liberation,
absorption, distribution, metabolism, and elimination are involved
to elicit the response.
Liberation is the first step in determining onset of action, rate of
absorption, availability, and so on.
In order for a drug to be absorbed, it must be present in the form of
solution; therefore, dissolution becomes the first and sometimes
rate-limiting step. This is true for all drug products by all routes of
administration, except intravenous (IV) route.
With all other routes of administration, the drugs must pass
membranes that act as lipid barriers.
Different transport mechanisms are employed to penetrate into and
to permeate through these membranes.
The various biopharmaceutic factors affecting bioavailability of
drugs are listed in Table below:
The LADMER system is key to the
following tasks:
Development of new active compounds, analogs, or derivatives;
Development of dosage forms with desired release characteristics;
Determination of pharmacokinetic parameters and
pharmacokinetic drug product profiles;
Determination and evaluation of bioavailability;
Selection of the most appropriate route of administration;
Determination of effective dose sizes; and
Adjustment of dosage regimen to achieve a desired therapeutic
concentration of drug in the body based on physiologic (e.g.,
body weight, age, sex) and pathologic factors.
Figure. Diagram of LADMER system showing the complex
interrelationships among drug,
drug product, and body.
Thank you