Absorption and drug

distribution Dr.S.VASANTH

Route with high bio availability ……….?

Transport across biological membrane ….?

Absorption of drug …….?

Distribution of drug ….?

Plasma proteins ……….?

Pre session

What is pharmacokinetics ?

ADME

What is pharmacokinetics ?

Transport across biological memberane

Lipid

Biological membrane

passive transport

Active transport

Facilitated diffusion

Symport

Antiport

Primary active transport

Secondary active transport

Biological membrane

pH of medium = pKa then drug is 50 % unionised and 50 % ionized

pH more than Pka medium is alkaline Acidic drugs ,ionization form increases and

nonionized decreases Basic drugs, unionized form increases and

ionized form decreases

Absorption is movement of the drug from its site of administration into the circulation

Different routes of drug absorption ?

Factors affecting drug absorption ?

Absorption

Lipid solublity /aqueous solublity

pH/pKA value

Gastric emptying /gut motility

Particle size and formulation

Food and presence of other substance /drug

Gastrointestinal disease

First pass metabolism

What is first pass metabolism ?

What is bioavailablity ?

Nitrates

Hydrocortisone

Lignocaine

Propanolol

Salbutamol

morphine

Drugs with high first pass metabolism

Rate and extent of a drug form the dosage form in unchanged form in the systemic circulation

Fraction of drug or percentage of drug reaches systemic circulation in unchanged form

Lipid solublity /ionization /pH Area of absorbing surface Blood circulation Gastric motility Presence of food Disease state of git

Factors affecting bioavailablity

First pass metabolism

Pharmaceutical factors

disintegration time

dissolution rate/time

Genetic influence's

Bioequvalance?

Phenytoin a(dilantin)

Phenytoin b (eptoin)

Apparent volume of distribution Volume in which drug appears to be

distributed ( apparent )if concentration throughout the body was same to that of the plasma

aVd= dose administered I.V /plasma concentration achieved

Distribution

Factors which affects the drug distributions

1). tissue permeability of drug a. physicochemical property – i) molecular

size ii) pKa iii) o/w partion

coefficient b. physiological barriers 2). Organ tissue size and perfusion rate 3). Binding of drug to tissue components a. with blood components b.with extravascular tissue proteins 4). Miscellaneous factors a. age b.Pregnancy d.Obesity e.Diet f.Disease states

g.Drug interaction

Redistribution ?

Plasma protein binding

Albumin

Alpha1 acid glycoproteins

Binding

Maintance of plasma concentration

Free and bound form measurement

Low vd- highly bound form

Long acting – highly bound

Not removed by hemodialysis

Displacement reaction

Hypoalbuminemia ,chirosis

Diazepam

Midazolam

Warfarin

Imipramine

cyclosporine

Drugs with high plasma protein binding

Bioavailablity 100% ……… ?

Bioequvalence ?.............

Volume of distribution ?

Significance of plasma protein binding ??

Post session