Absorption and bio availability of drugs

These slides describe the concept of Bioavailability and Bioequivalence. The factors affecting bioavailability also have been described

1. Absorption and Bioavailability Dr Naser Ashraf Tadvi Associate Professor Pharmacology

2. Absorption Sublingual Oral Subcutaneous and Intramuscular Topical

3. Bioavailability Definition Amount or percentage or fraction of drug that is absorbed from a given dosage form and reaches the systemic circulation in unchanged form. It refers to rate and extent of absorption of drug from its dosage form as determined by concentration-time curve in blood.

4. Bioavailability in various routes Route Bioavailability (%) characteristics intravenous 100(by definition) Most rapid onset intramuscular 75 to < 100 more painful subcutaneous 75 to < 100 Smaller volumes than IM; may be painful oral 5 to <100 Most convenient; first pass effect present rectal 30 to <100 Less first pass effect than oral inhalational 5 to <100 Often very rapid onset transdermal 80 to <100 Usually very slow absorption; lack of first pass effect; prolonged duration of action

5. Concentration Time Target concentration Drug A Drug B Drug C For BA two things are considered Rate & Extent Drug A is rapidly and completely absorbed…. B & C will be compared with it….. Drug C is slowly and completely absorbed…. Drug B is rapidly and incompletely absorbed….

6. PLASMA CONCENTRATION TIME CURVE Concentration Time 1 2 3 4 5 6 Drug A Drug B 7 8 9 1.Cmax  Peak(maximum) plasma concentration 2.Tmax  time at which maximum concentration is obtained 3.AUC (Area Under Curve) Minimum Effective Concentration Maximum safe concentration

7. Bioavailability = AUC after oral dose AUC after IV dose X 100 Cmax & Tmax measures the rate of absorption, AUC measures the extent of absorption.

8. Factors affecting absorption & bioavailability Drug related factors Dosage forms Salt form Crystal form Water of Hydration Particle size Nature of Excipients or adjuvants Degree of Ionization Pharmacological Factors pH GI transit time Disease conditions Presence of food and other substances First pass metabolism Drug- drug interaction Pharmacogenetic Factor Miscellaneous Route of Administration Area of absorbing surface Enterohepatic circulation State of circulation at site of absorption

9. Steps in Absorption Oral Administration of drug (Dosage form: Tab/Cap/Powder/Solution/Suspension) 1.Disintegration Tab. or Cap. fine particles 2.Dissolution Powders & Suspensions Drugs in Solution Solutions Available for Absorption through GIT

10. Drug related factors Better parameter

11. Drug related factors Salt form Salts of weakly acidic drugs are highly water soluble Crystal Form amorphous chloramphenicol palmitate, has better bioavailability compared to its crystalline forms Water of Hydration Anhydrous forms of caffeine, theophylline, have better bioavailability

12. Nature of excipients and Adjuvants Excipients are pharmacologically inert substances used as filling or binding agents Examples Starch Lactose Calcium sulphate Gum, Polysorbate-80(Wetting agent) Drug related factors

13. Drug related factor: Ionization Naser TAKE HOME MESSAGE …….. “ UNIONIZED FORM IS BETTER ABSORBED

14. Pharmacological Factors: pH Although acidic drug are better absorbed from stomach , a large portion of it gets absorbed through the intestine because of greater surface area it provides.

15. Gastric emptying time Naser

16. DISEASE CONDITIONS Naser

17. PRESENCE OF FOOD To be taken before meals To be taken after meals

18. PRESENCE OF OTHER AGENTS IRON ABSORPTION FAT SOLUBLE VITAMIN ABSORPTION REDUCED IN THE PRESENCE OF LIQUID PARAFFIN

19. ENTEROHEPATIC CIRCULATION Increases the bioavailability. Morphine Naser

20. Area of the absorbing surface and local circulation Naser

21. Pharmacogenetic factors Pharmacogenetics is the study of the genetic basis for variation in drug response. Slow acetylators of isoniazid, show increased bioavailability and are more subjected to toxicity

22. Chemical equivalent (Pharmaceutical equivalent) Drug formulations are said to be chemically equivalent if they contain same active ingredients and are identical in strength, concentration and dosage form

23. Bioequivalence Chemically equivalent drug formulations are considered to be bioequivalent when the rates and extent of bioavailability of active ingredients in the two formulations do not differ significantly when tested by standard procedures

24. Methods for delaying absorption Using slow release tablets, spansules depot inj. and subcutaneous implants. Change in physical characteristics of the drug Adding vasoconstrictor or applying tourniquet. Eg adrenaline with LA

25. Methods to facilitate absorption Adding hyaluronidase to the injection fluid increases rate of diffusion & greatly speeds up the drug absorption. Absorption from the site of injection may be increased by increasing the local blood flow.