1. Oral Drug Absorption

2. Most common route of administration
Anatomic and Physiologic consideration
Major processes in GI: secretion, digestion and absorption

3. Oral cavity: saliva, pH around 7, ptyalin (salivary amylase), mucin
Esophagus: pH of fluids 5-6, little drug dissolution, tablet lodging and irritation
Stomach: innervated by the vagus nerve, local nerve plexus, hormones, mechanoreceptors, chemoreceptors control gastric secretions and emptying.
Fasting pH 2-6, reduced in fed to 1.5-2
stomach acid secretionِ:gastrin and histamine
Stomach emptying

4. Doudenum: pH 6-6.5, optimum pH for enzymatic digestion of proteins and peptides
pancreatic juice: enzymes: trypsin, chymotrypsin, carboxypeptidases, amylase, pancreatic lipase
High absorption capacity
Jejunum
Ilium

5. Colon
lacks villi, limited drug absorption
more viscous and semisolid nature of lumen contents
lined with mucin: lubricant and protectant
pH: 5.5-7
Aerobic and anaerobic m.o.: drug metabolism
Residual area for drug absorption
Rectum
Small amount of fluid (2 ml) with pH of 7
Perfused by superior, middle and inferior hemorrhoidal veins

6. Drug absorption in the GIT
Passive diffusion is the main mechanism
Optimum site of absorption is the doudenum
large SA, high perfusion, availability of carrier mediated absorption mechanisms

7. Physiological Factors that Influence Drug Absorption from GIT
GI motility: Gastric emptying time and intestinal motility
GI perfusion
GI secretions
Presence of food

8. Gastrointestinal motility
Gastric emptying time
Rapid emptying into the stomach
Delay in gastric emptying would delay drug absorption (usually rate, possibly extent)
Very high intersubject variability
Factors that influence gastric emptying (table)

11. Liquids and small particles: rapid emptying
Large particles: delay is usually seen (3-6 hours due to food)
Non digestible solids: very slow emptying
Intestinal motility
Sufficient residency is needed for optimum absorption
Residency is 3-4 hours, could be prolonged in fed status (8-12 hours)
Intersubject variability is lower
Influenced by disease situation
Colon: 35 hours, influenced by diet

12. Drugs may influence intestinal transit: propanthelin
Metoclopromide
Laxatives
Disease states: Diarrhea (brief residency)

13. Effect of food and diet on bioavailability
Alteration in the rate of gastric emptying:delay in rate of absorption, Nitrofurantoin
Stimulation of gastric secretions
Competition between food components and drugs for specialised absorption mechanisms
Complexion of drugs with components in the diet
Increased viscosity of GI content and reduction in dissolution rate and diffusion to reach cell membranes
Timing of drug administration in relation to food is important

14. Intersubject variations General health of the individual
Gastrointestinal pH
Intersubject variations
General health of the individual
Localized disease situations (gastric and duodenal ulcers)
Types and amounts of food ingested
Drug therapy
Gastric pH may influence drug absorption in different ways:
Ionisation and solubility of acids and bases
Chemical stability of drugs in low gastric pH

15. Other gastrointestinal secretions
Bile and pancreatic secretions
Bile: pH
Bile salts, : bile salts, bilirubin, end products of haemoglobin break down, electrolytes, small amounts of cholesterol, phospholipids
Promote dissolution of lipophilic drugs and dosage forms
Promote membrane permeability (micelle formation)
Insoluble complexes (neomycin, kanamycin, vancomycin)
Pancreatic secretions
Enzymes: proteolytic activity

16. Drug stability in GIT
Chemical degradation.
Gut lumen metabolism
Gut wall metabolism
Bacterial metabolism
Hepatic metabolism

17. Factors influencing first pass metabolism
Age
Liver disease
Enzyme induction and inhibition
Induction: refampicin, smoking
Inhibition: cimetidine
Other miscellaneous factors that influence gastrointestinal absorption
Local disease states
Gastric surgery
Malabsorption
Chronic alcoholism
Chemotherapy

18. EFFECT OF DISEASE STATES ON DRUG ABSORPTION
Parkinson’s disease
Achlorhydric patients: weak-base drugs, dapsone, itraconazole, and ketoconazole
Congestive heart failure: reduced splanchnic blood flow, edema in the bowel wall

19. Inflammatory bowel diseases
Crohn’s disease: inflammatory disease of the distal small intestine and colon.
Acccompanied by regions of thickening of the bowel wall, overgrowth of anaerobic bacteria, and sometimes obstruction and deterioration of the bowel.
Effect on drug absorption is unpredictable (impaired absorption may occur)
Higher plasma propranolol concentration
Celiac disease: inflammatory disease affecting mostly the proximal small intestine
Increased rate of stomach emptying and increased permeability

20. Intestinal Infections:
Frequently cause diarrhea
Ampicillin and nalidixic acid, oral contraceptives

21. Gastric surgeries
Involve removal of part of the GIT: reduction in the epithelial surface area or changes in the motility or secretory patterns
Partial gastrectomy: reduced abs of some drugs
Resection of the small intestine
Colonic resection and loss of salfasalazine activity

22. Drugs that Affect Absorption of Other Drugs
Anticholinergics: Propantheline bromide: slow stomach emptying and motility of the small intestine.
Tricyclic antidepressants and phenothiazines: have anticholinergic side effects
Metoclopramide: stimulates stomach contraction, relaxes the pyloric sphincter, may reduce the effective time for the absorption, digoxin
Antacids
Cholestyramine