BIOPHARMACEUTICS

Definitions and Terminologies

Biopharmaceutics
The study of physical/ chemical properties of the drug, the dosage form (drug

product) in which the drug is given, the route of administration and the biological

effects they (drug) produce in terms of onset, duration and intensity.

 Biologic response
 Expressed as alteration of biologic process existing before drug was administered.

Magnitude is related to drug concentration achieved at receptor site.

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The observed effect of drug from a dosage form = inherent pharmacological

activity of the drug + its ability to reach the receptor site in appropriate

concentration.

Onset, intensity and duration of therapeutic effect drugs depend on biological +

dosage form factors.

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Factors Influencing the time course of a drug in plasma

The physical/chemical properties of the drug

Type of dosage form of the drug

Composition and method of manufacture of the dosage form

The size of the dose and frequency of administration of the dosage form

Site of absorption of the administered drug

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Co-administration of other drugs

Type of food taken by the patient

The disease state of the patient that may affect drug absorption, distribution and

elimination of the drug

The age of the patient

The genetic composition of the patient

PHARMACOKINETIC
After a drug is released from its dosage form, the drug is absorbed into the
surrounding tissue, the body, or both

It is the science of the kinetics of drug absorption, distribution, and elimination
(i.e., metabolism and excretion). The description of drug distribution and
elimination is often termed drug disposition

or

Simply it is the movement of drug within the body

PHARMACODYNAMIC
It is the study of the biochemical and physiological effects of drugs on the body.

A typical example of pharmacodynamics is how a drug interacts quantitatively

with a drug receptor to produce a response (effect).

Receptors are the molecules that interact with specific drugs to produce a
pharmacological effect in the body.

The pharmacodynamic effect, sometimes referred to as the pharmacologic

effect, can be therapeutic and/or cause toxicity.
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Often drugs have multiple effects including the desired therapeutic response as

well as unwanted side effects.

For many drugs, the pharmacodynamic effect is dose/drug concentration

related; the higher the dose, the higher drug concentrations in the body and the

more intense the pharmacodynamic effect up to a maximum effect.

It is desirable that side effects and/or toxicity of drugs occurs at higher drug

concentrations than the drug concentrations needed for the therapeutic effect.
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Clinical Pharmacokinetic
Clinical pharmacokinetics is the application of pharmacokinetic methods to drug therapy in
patient care.

It involves a multidisciplinary approach to individually optimized dosing strategies based on

 The patient’s disease state (e.g. renal, hepatic)

 Patient-specific considerations (e.g. genetics)

Population Pharmacokinetic
The study of pharmacokinetic differences of drugs in various population groups is termed
population pharmacokinetics.
Therapeutic Drug Monitoring
Clinical pharmacokinetic is also applied to therapeutic drug monitoring (TDM)

for very potent drugs, such as those with a narrow therapeutic range, in order

to optimize efficacy and to prevent any adverse toxicity.

 monitoring plasma drug concentrations (e.g., theophylline).

 monitoring a specific pharmacodynamic endpoint such as prothrombin clotting

time (e.g., warfarin).

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Some drugs frequently monitored are the aminoglycosides and anticonvulsants.

Other drugs closely monitored are those used in cancer chemotherapy, in order to

minimize adverse side effects.

Toxicokinetic
It is the application of pharmacokinetic principles to the design, conduct, and
interpretation of drug safety evaluation studies and in validating dose-related exposure
in animals.

Toxicokinetic data aid in the interpretation of toxicologic findings in animals and

extrapolation of the resulting data to humans.

Toxicokinetic studies are performed in animals during preclinical drug development

and may continue after the drug has been tested in clinical trials.

Clinical toxicology is the study of adverse effects of drugs and toxic substances
(poisons) in the body.
Measurement Of Drug Concentrations

Drug concentrations are an important element in determining individual or population

pharmacokinetics.

Drug concentrations are measured in biologic samples, such as

• Milk

• Saliva

• Plasma

• Urine

• others
Plasma level time curve after oral administration of drug
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The onset time corresponds to the time required for the drug to reach the MEC.

The intensity of the pharmacologic effect is proportional to the number of drug

receptors occupied, which is reflected in the observation that higher plasma drug

concentrations produce a greater pharmacologic response, up to a maximum.

The duration of drug action is the difference between the onset time and the

time for the drug to decline back to the MEC.

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The therapeutic window is the concentrations between the MEC and the MTC.

Drugs with a wide therapeutic window are generally considered safer than drugs

with a narrow therapeutic window.

Sometimes the term therapeutic index is used, which refers to the ratio between

the toxic and therapeutic doses.

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Peak plasma level (Cmax), is related to the dose, the rate constant for absorption,

and the elimination constant of the drug.

Time for peak plasma level (Tmax) is the time of maximum drug concentration in

the plasma and is a rough marker of average rate of drug absorption.

Area under the curve, or AUC, which is related to the amount of drug absorbed

systemically.
Branded Drug
A branded drug, is a medication sold by a pharmaceutical company under a

trademark-protected name.

Brand name medications can only be produced and sold by the company that

holds the patent for the drug or a drug that has a trade name and is protected by

a patent (can be produced and sold only by the company holding the patent).

Brand name drugs may be available by prescription or over the counter.

Generic drug

A generic must contain the same active ingredients as the original formulation.

According to the FDA, generic drugs are identical or within an acceptable

bioequivalent range to the brand name counterpart with respect to

pharmacokinetic and pharmacodynamic properties.

Generics are considered (by the FDA) identical in dose, strength, route of

administration, safety, efficacy, and intended use.

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Generic drugs marketed without brand names are generally less expensive than

brand-name drugs, even though they are chemically identical and meet the same

compendial standards of for safety, purity and effectiveness.

They can be legally produced if a patent has expired, or for drugs which have

never been patented.

The expiration of a patent removes the monopoly of the patent holder on drug

sales licensing.
Generic Equivalent

A drug product sold under its generic name whose active ingredients are identical

in chemical composition to one or more others sold under trademark. Inactive

ingredients may not be the same.

OR

The lawful act of a pharmacist, when exercised, of substituting one pharmaceutical

equivalent for another, in order to decrease the drug product cost.

Generic Substitution

The substituting of a generic drug for an identical brand drug, are chemically

equivalent, that has lost its patent protection is known as generic substitution.

Generic substitutions are less expensive and providing equivalent efficacy, safety,

side effect profile and dosing (with a few important exceptions).

Therapeutic
  alternative

Is a drug which differs chemically from prescribed drug but provides the same

effect when administered to patients.

OR 

A therapeutic alternative is a drug that is not chemically identical to a non-

preferred drug but has similar effects when given in therapeutically equivalent

doses.
Pharmaceutical Equivalents
For generic drug products to be pharmaceutical equivalents, they must be
identical dosage forms that contain identical amounts of the chemically identical
API.

Pharmaceutical equivalents deliver identical amounts of the API over the

identical dosing period.

They must meet the identical compendial or other applicable standards on

potency, content uniformity, disintegration times, and dissolution rates.
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Pharmaceutically equivalent drug products may contain different inactive

ingredients, or excipients, for example, colorant, flavor, and preservative.

They may contain different amounts of impurities within an allowable range.

This flexibility in compositions of the drug product sometimes, though rarely,
leads to undesirable consequences on the therapeutic performance.

In addition, pharmaceutically equivalent drug products may differ in

characteristics such as shape, release mechanism, scoring (for tablets),
packaging, and even labeling to some extent.
Pharmaceutical Alternatives
Drug products that contain the same therapeutic moiety or its precursor but
differ in dosage form, API amount, or chemical structure (different salt forms,
prodrugs, complexes, etc) are considered “pharmaceutical alternatives” by the
FDA if they meet applicable standards.

The route of administration should be the same for two products to qualify as
pharmaceutical alternatives.

For example, an IV injectable drug product cannot be a pharmaceutical

alternative to an oral tablet.
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In addition, capsule and tablets containing the same API, for example, quinidine

sulfate 200-mg tablets versus quinidine sulfate 200-mg capsules are considered

as pharmaceutical alternatives even if the products are bioequivalent.

BIOAVAILABILITY

According to 2003 FDA guidance,

Bioavailability is defined as the rate and extent to which the active ingredient or active
moiety is absorbed from a drug product and becomes available at the site of action.

For the products that are not intended to be absorbed into blood stream, bioavailability
may be assessed by measurement intended to reflect the rate and extent to which the
active ingredient or active moiety becomes available at the site of action.

In other words, it is the fraction of administered dose that reaches the systemic
circulation.
Purpose of Bioavailability
Primary stages of development of a suitable dosage for a new drug entity.

Development of a new formulations of the existing drugs.

Control of quality of a drug product during the early stages of marketing in order

to determine the influence of processing factors, storage and stability on drug

absorption.

Useful in determining the safety and efficacy of the drug product.

Bioequivalence

Two products are bioequivalent if

They are pharmaceutically equivalent.

Both rate and extent after administration in the same molar dose are similar to

such a degree that their effects can be expected to be essentially the same.