PHYSIOLOGIC AND DYNAMIC ATTRIBUTES OF GASTROINTESTINAL TRACT THAT INFLUENCE BIOAVALIABLITY

BIOAVAILABILITY …..• The relevant amount of an administered dose of

the particular drug that reaches the systemic circulation and the rate at which this occurs is known as bioavailability.

• It is usually less than 1 and its value is usually given in fraction.

• It is the fraction of drug that reaches systemic circulation in an unchanged form for biological effect following administration by any route .

• IV has 100% bioavailability.

FACTORS AFFECTING BIOAVAILABILITY IN GI TRACT

1. SURFACE

AREA

SURFACE AREA OF GI AVAILABLE FOR ABSORPTION• OESOPHAGUS :- when a drug is administered

orally it travel down through the esophagus because of its peristaltic contraction waver of the upper and lower sphincters and the related propulsive force which help the gravity .

• here no absorption takes place.

• STOMACH• Weakly acidic drug absorb good in stomach that is

due to The human stomach is capable of absorbing most acidic drugs and the very weakly basic drugs. Salicylic acid, aspirin, thiopental, etc. which are dissociated in the acidic gastric contents, are readily absorbed. Phenol red, quinine, etc. which are almost completely ionized in acid solution are not absorbed.

• SMALL INTESTINE :-• It has the largest surface area • The greater the surface area the greater will be

the absorption and bioavailability of drug .• Small intestine has large surface area due to

following reasons FOLDS OF KERECKRING. PRESENCE OF VILLI AND MICROVILLI.

2. GASTROINTESTINAL PH

GASTROINTESTINAL PH • It is an important consideration in absorption of

drug as PH effects the absorption of drug in 2 ways

Extent of ionization of the drug Chemical stability aspect of the drug

PH OF STOMACH

1-3.5FASTED

STATE3-7

FED STAT

E

• Gastric ph. returns to lower fasted state in 2-3 hrs. depending on size of the meal

• For example :- stomach has acidic PH so drug with opposite PH will be IONIZED and SOLUBLITY of that drug will be better

• But if the drug with same PH as that of stomach (taking as a example) will come in UNIONIZED form and will be ABSORBED better.

• Presence of food effects the absorption of drug as the presence of foods delays the absorption of some drugs such as TETRACYLNES,ACETAMINOPHEN etc.

• Whereas, on the other hand food may also increase the absorption of few drugs e.g. lipid soluble drugs

• As ANTACID increases the ph. that is due to the fact that they neutralize the acid in stomach and increases the PH .

ANTACIDS

H2 BLOCKE

RSINCREAS

ES PH

• BASIC drug absorbs better in SMALL INTESTINE because the PH rises along the length of small intestine ( due to the presence of bicarbonates secreted by small intestine ).

Presence of food

stimulates the flow of bile

which contain bile acids

ACT AS A SURFACTANTS

Involved in solubilization of fats and

hydrophobic drugs.

• The ph. drops up to 6.5 in colon due to :-

Bacterial enzymes

breakdown undigested carbohydrat

es

Convert them into

short chain fatty acids

Lowers the PH

3. Gastrointestinal MOTILITY- GASTRIC EMPTYING RATE

GASTROINTESTINAL MOTILITY• Gastrointestinal (GI) motility refers to the

movement of food from the mouth through the pharynx (throat), esophagus, stomach, small and large intestines and out of the body.

• That is for the drugs that are given orally.• With in the GI tract drug movement depends on

whether alimentary canal is in FED state or is In FASTED state.

MIGRATING MYOELECTRIC COMPLEX(MMC)• Gastric and small intestinal myoelectric and motor activity is

divided into two main patterns,

• During fasting, the predominant pattern of activity is the migrating myoelectric complex (MMC), a cyclically occurring pattern of electric and mechanical activity that is initiated in the stomach and duodenum almost simultaneously and, from there, propagates the length of the small intestine.

• The physiologic role of the MMC is to clear the stomach and small intestine of residual food, secretions, and desquamated cells and propel them to the colon. It basically empties the upper GIT to the cecum.

FASTED STATE FED

STATE

PHASES OF IMMC

PHASE 3INTENSE CONTRACTION

Contraction with higher amplitude, push the residual content down to

the alimentary canalDuration : 5-15 mins

PHASE 2IRREGULAR PHASEIncreased number of contraction

that are irregular Duration : 20-40 mins

PHASE 1Calm phaseInactive period ( alimentary canal

is quiescent) Duration : 30-60 mins

PHASE 4Reduction of

contraction leading to PHASE 1

DURATION “ 0-5 mins

FED STATE :- two activities has been observed in FED STATE1.

These phases mixes the content and move them towards the colon in short segment .

• 2. peristalsis

Contraction of distal stomach

Mix and breakdown

food particles

Move them towards pyloric

sphincter

FACTORS AFFECTING GASTRIC EMPTYING RATE• Composition of food.• Postural position.• Effect of drugs.• Effect of disease state.• Emotional state of a person.• exercise.

LUMINAL ENZYMES

LUMINAL ENZYMES• The enzymes present in the gastric juice are

called as luminal enzymes • following are the luminal enzymes:-

LipasesAmylasesProteasespepsin

They are responsible for nutrient digestion.

EXAMPLE ….• Azulfidine , a pro drug of 5-aminosalicylic acid

linked via an AZO bond to sulfapyridine• Sulfapyridine moiety makes the drug too large

and hydrophilic to be absorbed in the upper GIT and this permits its transport intact to the colonic region.

• The bacterial enzymes reduce the AZO bond and release the active drug 5 amino salicylic acid for local inflammatory bowel disease.

4. INTESTINAL MOTILITY

INTESTINAL MOVEMENTPROPULSIVE MOVEMENT

• it is known as up and down movement

• Causes crushing of dosage form.

• Determine intestinal transit rate and residence time of drug.

MIXING MOVEMENT• It is known as

segmentation movement.

• It causes movement of drug which is in solution form to the GI membrane.

• It facilitates dissolution of drug.

IMPORTANCE OF SITTT• Drugs that dissolve slowly in Small intestine and

absorb here, if intestinal motility is increased ,

• Drugs that are absorbed by intestinal carrier mediated transport system for them motility is very important .

• Enteric coated dosage form which release drug only when they reach the small intestine.

Drug rapidly MOVES in SI

Abs is decreas

ed

BIOAVALIABLITY IS

DECREASED

• Thickness of diffusion layer “h” • A/c to NOYES WHITNEY equation

• As, H is effected by Viscosity of FLUID Motility of GIT

High motility the “H” will be reduced and Dissolution will be increased that will Ultimately increase the Bioavailability