Introduction to biopharmaceutics and pharmacokinetics

Definition of Biopharmaceutics

Biopharmaceutics can be defined as the study of the

interrelationship of the physicochemical properties of the drug,

the dosage form in which the drug is given,

and the route of administration

on the rate and extent (amount) of systemic drug absorption.

Thus biopharmaceutics deals with the factors that influence the

1.       protection of the activity of the drug within the drug product (stability)

2.       the release of the drug from the a drug product

3.       the rate of dissolution of the drug at the absorption site, and

4.       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. 

Definition of Pharmacokinetics

Pharmacokinetics is defined as the study of rate processes involved in absorption, distribution, metabolism and excretion (ADME).

The study of pharmacokinetics involves both experimental and theoretical approaches.

The experimental approach involves

1.       the development of biological sampling techniques

2.       analytical methods development for the measurement of drugs and metabolites

3.       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.

Clinical pharmacokinetics is the application of pharmacokinetic methods in drug therapy.

This is a multidisciplinary approach where the dose of a drug is optimized for a specific patient depending on the disease state, age and sex of the patient. This subject requires information from medical and pharmaceutical research.

Population pharmacokinetics is the study of pharmacokinetic differences of drug in various population groups.

Therapeutic drug monitoring (TDM)

When drug with narrow therapeutic indices are used in patients, it is necessary to monitor plasma drug concentration closely by taking periodic blood samples. Some drugs those are frequently monitored are aminoglycoside antibiotics, convulsants and anticancer drugs in order to minimize adverse side effects.

Pharmacodynamics deals with the relationship between the drug concentration at the site of action (receptor) and pharmacologic response, including biochemical and physiological effects that influence the interaction of drug with the receptor.

Under pharmacodynamics we study the relationship between the plasma concentration of drug (related to the concentration at the site of action) and the magnitude of biological effect it shows.

Toxicokinetics

Toxicokinetics is the application of pharmacokinetic principles to the design, conduct and interpretation of drug safety evaluation studies and used in validating dose related exposure in animals. Toxicokinetic studies are conducted in animals and the result obtained is used to interpret possible toxic reactions in human.

The ultimate aim of a drug is to achieve optimal therapy.

1.       To attain this aim the drug is first molded into a suitable dosage form.

2.       The dosage form is administered in to the body through a suitable route of administration.

3.       The drug is released at the site of absorption at a certain rate.

4.       The drug is then absorbed from the site of absorption to systemic circulation.

5.       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.

6.       The drug produces its action at the site of action. The site of action may reside in some extravascular tissues.

7.       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.

Application of biopharmaceutics

1.       A company is going to market a new dosage form of a certain drug. The dose is known. When this dosage form is administered to a healthy human the drug may not released quickly. In this case the action of the drug will be delayed. In another case if the drug is released all at a time then the duration of action of the drug will be very short. So with the knowledge of biopharmaceutics we can change various formulation factors to obtain optimum onset of action and duration of action.

2.       A company is marketing tablets of a certain drug. Now it wants to change a few ingredients or some formulation factors. The new tablets may not behave similarly as the previous one. So the bioavailability of new tablets are compared with the old tablets. If it is found that the bioavilability of the newer tablets are equivalent (i.e bioequivalent)  to that of older tablets then the new tablets will be permitted to market (by FDA).

3.       A company is marketing the tablets of a certain drug. Now they have planned to make transdermal dosage form of the same drug. To establish its efficacy the bioavailability of the transdermal dosage form is compared to that of the established tablet dosage form. If both are found to be closer then the transdermal dosage form will be accepted by FDA.

Application of pharmacokinetics

1.       The bioavailabilty of a dosage form is calculated by pharmacokinetic equations.

2.       The frequency of dosing is calculated from pharmacokinetic equations.

3.       To calculate the dose of a controlled release dosage form pharmacokinetic equations are required.

4.       In case of patients with kidney failure the dose of a drug should be calculated very cautiously. If the rate of absorption of the drug is greater than the elimination rate of the drug from that patient then the drug will be accumulated in the body and may show toxic effect. The rate of elimination of the drug from the body of that patient is calculated with the help of pharmacokinetic equations.

5.       When a potent anticancer drug is administered to a patient the plasma concentration of the drug must be very close to minimum effective concentration. Since the therapeutic index of the drug is very narrow in case of potent drugs so rate of administration must also be very slow. This rate of administration is calculated by pharmacokinetic principles.