Tiêu đề 2. ABSORPTION OF DRUGS FROM GASTROINTESTINAL TRACT.pdf ✅

PHARMD GURU Page 1 ABSORPTION OF DRUGS FROM GASTROINTESTINAL TRACT I. DRUG ABSORPTION:  Drug absorption is defined as the process of movement of unchanged drug from the site of administration to systemic circulation.  Following absorption, the effectiveness of a drug can only be assessed by its concentration at the site of action.  However, it is difficult to measure the drug concentration at such a site. Instead, the concentration can be measured more accurately in plasma.  There always exist a correlation between the plasma concentration of a drug and the therapeutic response and thus, absorption can also be defined as the process of movement of unchanged drug from the site of administration to the site of measurement i.e. plasma. This definition takes into account the loss of drug that occurs after oral administration due to presystemic metabolism or first-pass effect.  A drug that is completely but slowly absorbed may fail to show therapeutic response as the plasma concentration for desired effect is never achieved. On the contrary, a rapidly absorbed drug attains the therapeutic level easily to elicit pharmacological BIOPHARMACEUTICS It includes: I. Drug absorption. II. Mechanism of drug absorption. III. Factors effecting drug absorption.
PHARMD GURU Page 2 effect. Thus, both the rate and the extent of drug absorption are important. Such an absorption pattern has several advantages: 1. Lesser susceptibility of the drug for degradation or interaction due to rapid absorption. 2. Higher blood levels and rapid onset of action. 3. More uniform, greater and reproducible therapeutic response. Figure: Plots showing significance of rate and extent of absorption in drug Drugs that have to enter the systemic circulation to exert their effect can be administered by three major routes: 1. The Enteral Route: includes peroral i.e. gastrointestinal, sublingual/buccal and rectal routes. The GI route is the most common for administration of majority of drugs. 2. The Parenteral Route: includes all routes of administration through or under one or more layers of skin. While no absorption is required when the drug is administered i.v., it is necessary for extravascular parenteral routes like the subcutaneous and the intramuscular routes.
PHARMD GURU Page 3 3. The Topical Route: includes skin, eyes or other specific membranes. The intranasal, inhalation, intravaginal and transdermal routes may be considered enteral or topical according to different definitions. Below table compares the bioavailability/absorption pattern and advantages and disadvantages of drugs administered by common routes. ROUTE BIOAVAILABILITY ADVANTAGES DISADVANTAGES PARENTERAL Intravenous (IV)  Complete (100%) systemic drug absorption.  Drug is given for immediate or controlled effect.  May inject large fluid volumes.  Suitable for irritating drugs  Increased chance for adverse reaction.  Possible anaphylaxis.  Requires skill in insertion of infusion set.  Tissue damage at site of injection (infiltration, necrosis, or sterile abscess). Intramuscular injection (IM)  Rapid absorption from aqueous solutions.  Slow absorption from non-aqueous (oily) solutions.  Easier to inject than intravenous injection.  Larger volumes may be used compared to subcutaneous solution.  Irritating drugs may be very painful.  Variable rates of absorption depending upon muscle group injected and blood flow. Subcutaneous injection (SC)  Rapid absorption from aqueous solution.  Slow absorption from depot formulations  Generally, used for vaccines and drugs not absorbed orally e.g. insulin.  Rate of drug absorption depends upon blood flow and injection volume ENTERAL ROUTES Buccal or sublingual (SL)  Rapid absorption of lipid- soluble drugs.  No presystemic metabolism.  Some drug may be swallowed. Not for most drugs or drugs with high doses. Oral (PO)  Absorption may vary. Generally slower absorption rate compared to IV bolus or IM injection.  Safest and easiest route of drug administration.  Suitable for both immediate-release and modified release drug products.  Some drugs are unstable in GIT, or undergo presystemic metabolism or show erratic absorption. Rectal (PR)  Absorption may vary from suppository.  More reliable absorption from enema (solution).  Useful when patient cannot swallow medication.  Used for local and systemic effects.  Absorption may be erratic. Suppository may migrate to different position.  Some patient discomfort
PHARMD GURU Page 4 OTHER ROUTES Transdermal  Slow absorption, rate may vary.  Increased absorption with occlusive dressings.  Transdermal delivery system (patch) is easy to use and withdraw.  Continuous release for a specified period.  Used for lipid soluble drugs with low dose and low MW.  Low presystemic metabolism.  Some irritation by patch or drug.  Permeability of skin variable with condition, anatomic site, age, and gender.  Type of cream or ointment base affects drug release and absorption. Inhalation  Rapid absorption.  Total dose absorbed is variable.  May be used for local or systemic effects.  Particle size of drug determines anatomic placement in respiratory tract.  May stimulate cough reflex.  Some drug may be swallowed. GASTROINTESTINAL ABSORPTION OF DRUGS The oral route of drug administration is the most common for systemically acting drugs and therefore, more emphasis will be given to gastrointestinal (GI) absorption of drugs. Moreover, it covers all the aspects of variability observed in drug absorption. Before proceeding to discuss absorption aspects, a brief description of cell membrane structure and physiology is necessary. CELL MEMBRANE: STRUCTURE AND PHYSIOLOGY For a drug to be absorbed and distributed into organs and tissues and eliminated from the body, it must pass through one or more biological membranes/barriers at various locations. Such a movement of drug across the membrane is called as drug transport. The basic structure of cell membrane is shown in Fig below: