Biopharmaceutics &
Pharmacokinetics
Satish C S, Ph.D.
Department of Pharmaceutics
Biopharmaceutics & Pharmacokinetics
Absorption & Distribution
Biological Factors influencing drug absorption though GIT
Unit 1, Class 5
Satish C S, Ph.D.
Department of Pharmaceutics
Biopharmaceutics & Pharmacokinetics
Biological Factors
1. Surface area of gastrointestinal absorption sites
• The total absorptive area of the small intestine, composed
largely of microvilli has been calculated to be about 200 m2
and an estimate of 1 litre of blood passes through the
intestinal capillaries each minute.
• The corresponding estimates for the stomach are only
0.1 m2 to 0.2 m2 and 150ml/min.
Biopharmaceutics & Pharmacokinetics
Biological Factors
1. Surface area of gastrointestinal absorption sites
• Permeability tends to decrease progressively from
duodenum to colon resulting in decrease in the kinetics of
absorption.
• The low peristaltic movement, long transit time and high
permeability make intestine the best site for absorption of
most drugs.
Biopharmaceutics & Pharmacokinetics
Biological Factors
2. Gastro Intestinal Blood Flow
• The high blood flow rate within the GI tract helps to maintain
concentration gradient across the epithelial membrane for
continued absorption.
• The circulating blood rapidly removes the drug from absorption site
thus providing “Sink” conditions.
Biopharmaceutics & Pharmacokinetics
Biological Factors
Biopharmaceutics & Pharmacokinetics
Biological Factors
3. Gastric emptying rate and motility
• The gastric emptying of fluids and small particles is a first
order exponential process, i.e. the rate of gastric
emptying is proportional to the volume of material
remaining in the stomach.
• Gastric emptying rate is the rate at which the gastric contents empty
into the small intestine.
• Gastric emptying time is the time required for the gastric contents to
empty into the small intestine.
Biopharmaceutics & Pharmacokinetics
Biological Factors
3. Gastric emptying rate and motility
• Most drugs are optimally absorbed from the small
intestine,
• hence any reduction in rate at which drug leaves the
stomach and enters the duodenum is likely to reduce the
overall rate of drug absorption and delay the onset of
therapeutic response.
Biopharmaceutics & Pharmacokinetics
Biological Factors
Factors Affecting Gastric Emptying
Biopharmaceutics & Pharmacokinetics
Biological Factors
Factors Affecting Gastric Emptying
Viscosity Rate of emptying is greater for less viscous solutions
Emotional - Stressful emotional states increase stomach contraction
states and emptying rate
- Depression reduces stomach contraction and emptying
Disease states Rate of emptying is reduced in: Some diabetic patients,
hypothyrodism
Rate of emptying is increased in: hyperthyrodism
Excercise Reduce emptying rate
Biopharmaceutics & Pharmacokinetics
Biological Factors
4. Effect of Food:
A- Complexation of drugs with components in the diet
e.g. Tetracycline forms non-absorable complexes with calcium and
iron, and thus it is advised that patients do not take products
containing calcium or iron, such as milk, iron preparations or
indigestion remedies, at the same time of day as the tetracycline.
Biopharmaceutics & Pharmacokinetics
Biological Factors
B- Alteration of pH
Food tends to increase stomach pH by acting as a buffer.
This liable to decrease the rate of dissolution of a weakly basic
drug and increase that of a weakly acidic one.
Biopharmaceutics & Pharmacokinetics
Biological Factors
C- Alteration of gastric emptying
Fats and some drugs tend to reduce gastric emptying and thus
delay the onset of action of certain drugs.
Biopharmaceutics & Pharmacokinetics
Biological Factors
D- Food-induced changes in presystemic metabolism
- E.g. Grapefruit juice is capable of inhibiting the intestinal
cytochrome P450 (CYP3A) and thus taken with drugs that are
susceptible to CYP3A metabolism which result in increase of
their bioavailability.
Medicines affected by grapefruit
• Statins. Statins are medicines that lower your cholesterol.
• Calcium channel blockers.
• Anticoagulants.
• Antiplatelet medicines.
• Cyclosporin and immunosuppressants
Biopharmaceutics & Pharmacokinetics
Biological Factors
5. Gastrointestinal pH
• Gastric fluid is highly acidic, exhibiting a pH within the
range 1 to 3; fluid in small intestine has a pH range of 5-8
whereas that in colon has pH of about 8.
• There is considerable variation in GI pH depending upon
factors like localized disease in GI tract e.g. ulcer, the
food ingested, drug therapy & diurnal cycle.
Biopharmaceutics & Pharmacokinetics
Biological Factors
6. Drug Stability in the GI tract
• A drug may be chemically degraded and metabolized in the
gastrointestinal tract.
• Chemical degradation, particularly, pH dependent reactions
such as hydrolysis can occur in the fluids of the GI tract e.g.
erythromycin undergoes acid catalyzed hydrolysis in gastric
fluid.
Biopharmaceutics & Pharmacokinetics
Biological Factors
7. Hepatic Metabolism and First Pass Effect
• All drugs that are absorbed through gastrointestinal lumen, pass into the
hepatic portal system and are presented to the liver before reaching
systemic circulation.
• This passage of absorbed drug through the liver may result in the extensive
metabolism of drug before it reaches the systemic circulation.
Biopharmaceutics & Pharmacokinetics
Biological Factors
7. Hepatic Metabolism and First Pass Effect
• This phenomenon known as ‘First Pass Effect’ results in a
decrease in bioavailability of those drugs that are rapidly
metabolized by the liver.
• The bioavailability of susceptible drug may be reduced to such
an extent as to make it ineffective by oral route e.g. lignocaine.
Notable drugs that experience a significant first-pass effect are imipramine,
morphine, propranolol, buprenorphine, diazepam,, cimetidine, lidocaine, and
chlorpromazine.
Satish C S, Ph.D.
Chairperson, Department of Pharmaceutics
satishcs@[Link]
