1. Factors affecting Drug Absorption (Physiological factors)
SALMAN BIN ABDUL AZIZ UNIVERSITY
COLLEGE OF PHARMACY
Factors affecting Drug Absorption (Physiological factors)
PHARMACEUTICS- IV
(PHT 414 )
Dr. Mohammad Khalid Anwer, Ph.D
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2. Physiological factors Physicochemical or Pharmaceutical
Absorption of drug from Non-per oral route.
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3. Physiology of GIT
GIT comprises of no. of components, Stomach Small Intestine Large Intestine The primary functions of GIT are Secretion Digestion Absorption.
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4. Physiological factors
1.Age Gastric Empting Intestinal Transit GI pH Blood Flow to GIT Diseased State GI Content First pass effect
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5. 1. Age
In infants GI pH is high and intestinal surface and blood flow to GIT is low as compared to adults results in poor drug absorption.
In elderly people, alteration in drug absorption becuase of alteration in gastric emptying, and incidents of achlorhydria and bacterial over growth in small intestine.
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6. 2. Gastric emptying
Defined, as passage of contents of stomach into the intestine.
Rapid gastric emptying is advisable where:
Rapid onset action is required, eg; sedatives.
Dissolution of drug occurs in intestine eg; Enteric coated tablets.
Drug is unstable in gastric fluids.
Drug is best absorbed from distal part of small intestine, eg vitamin B 12 .
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7. Kinetics of GI emptying
GI emptying is first-order kinetics many parameters are used to quantify a gastric emptying; 1.Gastric emptying rate: Is the speed at which the stomach contents are emptied into the intestine. 2.Gastric emptying time: Time required for the GI content to empty into small intestine. 3.G.E.t1/2: Is time taken for half the stomach contents to empty.
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8. Factors affecting GI emptying
1.Volume of meals Composition of meal Physical state of meal GI ph Body posture Emotional state Exercise Drugs
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9. 1.Volume of meal: Larger the bulk of the meal, longer the gastric time and however an initial rapid rate of emptying is observed with large meal volume and initial lag phase in emptying of small volume meals. 2.Composition of meal: The rate of gastric emptying for various food materials in the following order carbohydrates>proteins>fats. 3.Physical state: Liquid meal takes less time as compared to solid meals. 4.GI ph: Gastric emptying is retarded at low stomach pH and promoted at alkaline pH.
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10. 5. Exercise: Vigorous physical training retards gastric empting. 6
5.Exercise: Vigorous physical training retards gastric empting. 6.Body posture: Gastric emptying is favored while standing and by lying on right side. 7. Emotional state: Stress and anxiety promotes GI motility, where as depression retards it. 8.Drugs: That retards gastric emptying are antacids, anti cholinergic, narcotic analgesics and tri cyclic antidepressants. And metoclopramide, domperidone and cisapride stimulate gastric emptying.
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11. 3. Intestinal transit
Defined as, the residence time of drug in small intestine. Delayed intestinal transit is desirable for: 1.Sustained release dosage forms, 2.Drug that only release in intestine ie ,enteric coated formulations, 3.Drugs absorbed from specific sites in intestine, eg; several B vitamins
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12. 4. GI pH
GI pH influence in several ways: 1.Disintegration: Disintegrating of some dosage forms is pH sensitive, enteric coated tabs dissolve only in alkaline pH. 2.Dissolution: A large no. of drugs either weak acids or weak bases, their solubility is greatly affected by GI pH. -weakly acidic drugs dissolve rapidly in alkaline pH. -basic drugs soluble in acidic pH.. 3.Absorption: Depending upon drug pKa whether its an acidic or basic drug the GI pH influences drug absorption. 4.stability of drug: GI pH influence the stability of drug. Eg; erythromicin
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13. 5. Blood flow to GIT
GIT is extensively supplied by blood capillary, about 28% of cardiac output is supplied to GIT portion, most drug reach the systemic circulation via blood only. Any factor which affects blood flow to GIT may also affect absorption.
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14. 6. Disease state
Several disease state may influence the rate and extent of drug absorption.
Three major classes of disease may influence bioavailability of drug.
GI diseases
CVS disease
HEPATIC disease
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15. GI diseases A. GI infections :
1.Celiac disease: (characterized by destruction of villi and microvilli) abnormalities associated with this disease are increase GI emptying rate and GI permeability, alter intestinal drug metabolism.
2.Crohn’s disease: alter gut transit time and decreased gut surface area.
B. GI surgery:
Gastrectomy may cause drug dumping in intestine, osmotic diarrhoea and reduce intestinal transit time.
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16. CVS diseases Hepatic diseases
In CVS diseases blood flow to GIT decrease, causes decreased drug absorption.
Hepatic diseases
Disorders like hepatic cirrhosis influences bioavailability of drugs which under goes first pass metabolism.
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17. 7. Gastro intestinal contents
1.Food- drug interaction: In general presence of food either delay, reduce, increase or may not affect absorption.
Aspirin Delayed
Penicillin's Decreased
Griseofulvin Increased
Methyldopa Unaffected
2.Interaction of drug with normal GI contents: GIT contains no. of normal constituents such as mucin, bile salts and enzymes, which influence the drug absorption. Eg; Inhibitory action of bile on GI motility.
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18. 3.Drug-Drug interaction in the GIT: Physico chemical drug- drug interaction: Adsorption: Eg; anti diarrhial preparations contains adsorbents like kaolin, prevents a absorption of many drugs co-administered with them. Complexation: Eg; penicillin derivative with ca-gluconate. pH changes: Basic drugs changes gastric pH Eg; tetracycline with antacids
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19. 8. First pass metabolism
Four primary systems which affect pre systemic metabolism of a drugs Luminal enzymes Gut wall enzymes or mucosal enzymes Bacterial enzymes Hepatic enzymes.
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20. Lumenal enzymes: These are enzymes present in gut fluids and include enzymes from intestinal and pancreatic secretions.
Gut wall enzymes: Also called mucosal enzymes they are present in gut and intestine, colon.
Bacterial enzymes: GI microflora scantily present in stomach and small intestine and is rich in colon.
Hepatic enzyme: several drug undergo first-pass hepatic metabolism, highly extracted ones being isoprenaline, nitroglycerin, morphine etc.
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21. THANK U
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