BIOAVAILABILITRY

Dr. Muslim Suardi, MSi., Apt. Faculty of Pharmacy University of Andalas

Bioavailability

“The rate & extent to which the active ingredient or active moiety is absorbed from a drug product & becomes available at the site of action

Usually estimated by its concentration in body fluids, pharmacologic response, clinical response, the rate & extent of excretion

Bioavailability Concerned with how quickly & how

much of a drug appears in the blood after a specific dose is administered

The BA of a drug product often determines the therapeutic efficacy of that product since it affects the onset, intensity & duration of therapeutic response of the drug.

Absolute & Relative BA Determination of absolute

BA of a drug usually involves a comparison of AUC obtained following extravascular & IV administration of the drug

Relative BA is obtained by

comparing the AUCs when like or unlike dosage forms of the same drug are administered by same or different routes but not iv.

Absorption

Occurs after its release from the dosage form. Release of drug depends on the physical & chemical properties of the drug, the dosage form (delivery system), the site & route of administration.

The physical & chemical characteristics of a drug as well as its formulation are of prime importance in BA because they can affect not only the absorption characteristics of the drug but also its stability.

Absorption Since a drug must be dissolved to be

absorbed, its rate of dissolution from a given product must influence its rate of absorption, the onset, & could affect the pharmacologic activity of a drug.

Factors that affects the dissolution rate of slowly dissolving substances is the surface area of the dissolving solid

After the administration of a drug solution, or following the dissolution of a solid dosage form, drug molecules enter into the systemic circulation by crossing one or more biological membranes.

Absorption

Effects of formulation & processing variables on the dissolution of active ingredients from drug products; an apparently inert ingredient may affect drug absorption.

The nature of the dosage form itself may have an effect on drug absorption characteristics.

Fastest availability

Slowest availability

SolutionsSuspensionsCapsulesTabletsCoated tabletsControlled-release formulations

FACTORS INFLUENCE THE BA OF A DRUG

BA Factors related to the dosage formPhysicochemical properties

of the drug

Formulation & manufacturing variables

Particle sizeCrystalline structureDegree of hydration of crystalSalt or ester form

Amount of disintegrantAmount of lubricantSpecial coatingsNature of diluentCompression force

Factors influence the BA of a drug

BA Factors Related to the patient

Physiologic factors Interactions with other substances

Variations in absorption power along GI tractVariations in pH of GI fluidsGastric emptying rateIntestinal motilityPerfusion of GITPresystemic & first-pass metabolismAge, sex, weightDisease states

FoodFluid volumeOther drugs

METHODS TO ASSESS BA

Sequence of events after

administration of a drug product

Method of evaluation Example

Dissolution at administration or absorption site

Dissolution rate In vitro: water, buffer, artificial gastric fluid, artificial intestinal fluid, artificial saliva, artificial rectal fluid

Free drug in systemic circulation

Blood level time profile, Peak blood level, Time to reach peak, Area under blood level time curve

In vivo: whole blood, plasma, serum

Pharmacologic effect Onset of effect, Duration of effect , Intensity of effect

In vivo: discriminate measurement of pharmacologic effect (blood pressure, blood sugar, blood coagulation time)

Clinical response Controlled clinical blind or double-blind, Observed clinical success or failure

In vivo: evaluation of clinical responses

Elimination Cumulative amount of drug excreted, Maximum excretion rate, Peak time of excretion

In vivo: urine