DRUG ABSORPTION AND DISTRIBUTION OF DRUG Objective/ Learning outcome: Define the 4 basic drug disposition mechanism Describe routes of drug administration. Describe drug distribution, elimination, metabolism and excretion in the body.

Meaning of Drug Absorption and Distribution: Unless a drug acts topically (i.e. at its site of application) it first must enter the blood and then be distributed to its site of action. The mere presences of a drug in the blood, however, does not lead to pharmacological response. To be effective, the drug must leave the vascular space and enter the intercellular or intracellular spaces or both. The rate at which a drug reaches its site of action depends on its rate of absorption and distribution. Absorption involves the passage of the drug from its site of administration into the blood; distribution involves the delivery of the drug to the tissue.

For a drug to reach its site of action after administration a drug must cross a number of biological barriers and membranes, which are predominantly lipid in nature. Competing processes such as binding to plasma proteins, tissue storage,metabolism,and excretion determine the amount of drug finally available for interaction with receptors.

Mechanism of movement of drug molecules across cell barriers: Diffusion through lipids: The number of molecule crossing the membrane per unit area in unit time is determined by the permeability coefficient and the concentration difference across the membrane Solubility of the drug in the membrane and diffusivity plays an important role. pH and ionisation, pH partition and ion trapping plays active in drug crossing the membrane.

Carrier-mediated transport: Many cell membrane posses specialized transport mechanism that regulates entry and exit of physiologically important molecules such as sugar, amino acids neurotransmitters and metal ions. This transport system involves a carrier molecules. These could be in the form of facilitated diffusion or active transport. Other factors are binding of drug to plasma protein and partition into body fat and other tissue.

DRUG DISPOSITION: Drug disposition is the basic process that influence the overall behavior of drug molecules in the body, it can be divided into four: Absorption Distribution Metabolism Excretion (elimination). Drug Absorption : is the passage of drugs from its site of administration into the plasma. This is important in all routes of administration except intravenous and inhalation.

Routes of administration ORAL ADMINISTRATION: Most drugs are taken by mouth and swallowed, Little absorption occurs until the drug enters the small intestine. Drugs absorption in the intestine is by passive transfer, by ionization and lipid solubility of drug molecules. Factors affecting intestinal absorption include : GI motility, Splanchnic blood flow, particle size formation and physiochemical factors.

Bioavailability is the term used to indicate the proportion of drug that passes into the systemic circulation after oral administration, taking into account both absorption and local metabolic degradation. Bioequivalence is evidence that the new product behaves sufficiently similarly to the existing one to be substituted for it without causing clinical problems.

SUBLINGUAL ADMINISTRATION: This is administration under the tongue for absorption directly in the oral cavity. This is useful sometimes when drugs is either unstable at gastric pH or rapidly metabolized by the liver or when rapid response is needed. e.g. glycerol trinitrate. These drugs pass directly into the systemic circulation without entering the portal system.

RECTAL ADMINISTRATION: Rectal administration is used for drugs that are required either to produce local effect or to produce systemic effects. Absorption following rectal administration is often unreliable, but this route can be useful in patients who are vomiting or are unable to take medication by mouth. TOPICAL APPLICATION: Cutenous: when local effect on the skin is needed. Eye drop: absorption through the conjunctiva to produce effect on the eye. Nasal sprays: use in the nasal to produce effect in nasal-associated lymphoid tissue.

INHALATION: Routes used for volatile and gaseous drugs e.g. anesthesia). Here the lungs act as both the route of administration and excretion. Most drug given to affect the lungs are also given by inhalation e.g. glucocorticords (beclomethazone) and bronchodilators (salbutamol). They are given to achieve much higher concentration in the lungs than elsewhere in the body, therefore minimizing side effects.

Subcutaneous: under the skin. PERENTERAL ADMINISTRATION Intravenous : directly into the veins, it is the fastest and most certain route of administration. But has more side effects. Subcutaneous: under the skin. Intrathecal: into the sub arachnoids space via lumber puncture needle is used for some specialized purpose e.g. methrotrixate in treating some childhood leukemia, regional anesthesia by injection of local anesthetic e.g. bupivacain. Intramuscularly : into the muscles.

DISTRIBUTION OF DRUGS IN THE BODY Body fluid compartments. Blood brain barrier Volume of distribution Vd = Q/Cp

SPECIAL DRUG DELIVERY STSTEMS. Several approaches are being explored in an attempt to improve drug delivery. They include -: biological erodable microshpere pro-drug antibody –drug conjugates packing in liposomes coating implantable devices.

END OF LECTURE 4 THANK YOU