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Pharmacokinetics I Drug administration and absorption Prof. Hanan Hagar Pharmacology Department

Pharmacokinetics I Drug administration and absorption Prof. Hanan Hagar Pharmacology Department. Pharmacokinetics. By the end of this lecture, the student should be able to Discuss the different routes of drug administration

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Pharmacokinetics I Drug administration and absorption Prof. Hanan Hagar Pharmacology Department

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  1. Pharmacokinetics I Drug administration and absorption Prof. Hanan Hagar Pharmacology Department

  2. Pharmacokinetics By the end of this lecture, the student should be able to • Discuss the different routes of drug administration • Identify the advantages and disadvantages of various routes of drug administration • Know the various mechanisms of drug absorption • List different factors affecting drug absorption

  3. Recommended books • Lippincott’s illustrated reviews (Pharmacology) by Howland and Mycek • Basic and Clinical Pharmacology by Katzung

  4. Pharmacokinetics of drugs (ADME) Are studies of ADME of drugs • Absorption • Distribution • Metabolism • Excretion

  5. Drug Pharmacokinetics Excretion Metabolism Administration Blood Site of action Absorption Different organs & tissues Distribution

  6. Absorption & distribution Elimination Sites of Administration

  7. Routes of drug administration • Enteral via gastrointestinal tract (GIT). • Oral • Sublingual • Rectal • Parenteral administration = injections. • Topical application • Inhalation

  8. Oral administration

  9. First pass Metabolism • Drugs taken orally are first taken to liver (via portal circulation) where they are metabolized before reaching to rest of body via general circulation. • so the amount reaching blood circulation is less than the amount absorbed

  10. First pass Metabolism Where first pass metabolism can happen? • Liver • Gut wall • GIT Lumen What are results of first pass metabolism? • Low bioavailability of drugs = low serum level of active drug that can produce action. • Short duration of action of drugs (t ½).

  11. First pass effect

  12. Oral Dosage Forms (oral formulations) • Tablets (enteric coated tablets that dissolve only in intestine). • Capsules (hard and soft gelatin capsules). • Syrup • Suspension (mixture of insoluble solid in a liquid) • Emulsion (mixture of two immiscible liquids)

  13. Tablets Spansule Soft- gelatin capsule Hard- gelatin capsule

  14. Sublingual

  15. Rectal administration

  16. Parenteral administration Intradermal (I.D.) (into skin) Subcutaneous (S.C.) (under skin) Intramuscular (I.M.) (into muscles) Intravenous (I.V.) (into veins) Intra-arterial (I.A.) (into arteries) Intrathecal (I.T.) (cerebrospinal fluids ) Intraperitoneal (I.P.) (peritoneal cavity)

  17. Intravenous administration

  18. Single use Repeated use Ampoule Vial

  19. Topical application • Drugs are applied to skin, ear, eye, nose, vagina, • Usually used to provide local action. • No first pass metabolism. • Used for lipid soluble drugs • Drugs can be applied to • Skin (percutaneous administration) e.g. topical local anesthesia • Eye drops e.g. conjunctivitis • Ear drops e.g. otitis externa • Intranasal, e.g. decongestant nasal spray

  20. a medicated adhesive patch applied to skin to provide systemic effect (prolonged drug action) e.g. the nicotine patches Transdermal patch

  21. Inhalation

  22. Nebulizer Atomizer

  23. Drug absorption Is the passage of drug from its site of administration to its site of action through cell membranes. Cell membrane Sites of Administration Sites of action

  24. Mechanisms of drug absorption • Simple diffusion = passive diffusion. • Active transport. • Facilitated diffusion. • Pinocytosis (Endocytosis).

  25. Cell membrane

  26. Simple or passive diffusion • water soluble drug(ionized or polar) is readily absorbed via diffusion through aqueous channels or pores in cell membrane. • Lipid soluble drug(nonionized or non polar) is readily absorbed via diffusion through lipid cell membrane itself.

  27. Simple diffusion

  28. Simple diffusion Low conc High conc

  29. Simple diffusion Characters • common. • Occurs along concentration gradient. • Requires no energy • No carrier is needed • Non selective • Not saturable • Depends on lipid solubility. • Depends on pka of drug - pH of medium.

  30. Simple diffusion Drugs exist in two forms ionized (water soluble) nonionized forms (lipid soluble) in equilibrium. Drug ionized form + nonionized form • Only nonionized form (lipid soluble) is absorbable. • The ratio between nonionized form / ionized form is determined by pH of the medium and pKa of the drug.

  31. pKa of the drug (Dissociation or ionization constant): is defined as pH at which half of the substance is ionized & half is unionized. • The lower the pKa value of the acidic drug the stronger the acid e.g aspirin (Pka= 3.0 ). • The higher the pKa value of a basic drug, the stronger the base e.g propranolol ( pKa= 9.4)

  32. pH of the medium Affects degree of ionization of drugs. Weak acids  best absorbed in stomach. • weak acid drug will exist mainly in its unionized form (lipid soluble form) in an acidic medium and can be more readily absorbed from the stomach into the systemic circulation. Weak bases  best absorbed in intestine. • Basic drugs are more ionized and less absorbable in acidic medium. On the contrary, basic drugs are more lipid soluble (nonionized) and more absorbable in an alkaline medium.

  33. Which one of the following drugs will be best absorbed in stomach (pH=3)? Aspirin pka=3.0 warfarin pka=5.0 Arrange the following drugs in ascending order from least to greatest in rate of absorption in small intestine (pH=7.8)? Propranolol pka= 9.4 Aspirin pka=3.0 warfarin pka=5.0 Answer: Aspirin (the least aborption), warfarin, propranolol (the greatest absorption).

  34. Active Transport • Relatively unusual. • Occurs against concentration gradient. • Requires carrier and energy. • Specific • Saturable. • Iron absorption. • Uptake of levodopa by brain.

  35. Carrier-mediated Facilitated Diffusion • Occurs along concentration gradient. • Requires carriers • Selective. • Saturable. • No energy is required.

  36. Phagocytosis (Endocytosis & Exocytosis) Endocytosis: uptake of membrane-bound particles. Exocytosis: expulsion of membrane-bound particles. Phagocytosis occurs for high molecular weight Drugs or highly lipid insoluble drugs.

  37. (Exocytosis) (Endocytosis) OUT IN IN OUT

  38. Factors modifying drug absorption GENERAL FACTORS • Lipid solubility • Degree of ionization • Drug solubility (aqueous sol better than oily, susp, sol) • Dosage forms (depending on particle size and disintegration) • Concentration of drugs • Circulation at site of absorption • Area of absorbing surface • Route of administration.

  39. Mechanisms of drug absorption

  40. Summary • Different routes of administration are available. • Parenteral administration is the suitable route to provide rapid effect. • IV is used in emergency and provide high availability. • Oral administration is best avoided during emergency or when severe first pass metabolism may occur. • Drugs may cross any cell membrane by simple diffusion, active transport, facilitated diffusion, and pinocytosis.

  41. Questions?

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