OIA1013 DRUG ABSORPTION

Understanding Drug Absorption and Its Influencing Factor

Introduction to Drug Absorption

Definition and Importance

Drug absorption refers to the movement of drugs from the site of administration into the central compartment of the body, which is crucial for pharmacokinetics (ADME: Absorption, Distribution, Metabolism, Excretion).

It is essential to differentiate drug absorption from drug bioavailability; while absorption focuses on the movement of the drug, bioavailability measures the extent and rate at which the active ingredient or active moiety is absorbed and becomes available at the site of action.

Various routes of drug administration include oral, transdermal, inhalational, intramuscular, and subcutaneous, each with unique absorption characteristics.

Mechanisms of Absorption

Absorption primarily occurs in the small intestine, which has the largest surface area for drug absorption due to structures like plicae circularis and villi that increase surface area by tenfold.

Drug absorption can occur through three mechanisms: passive diffusion of lipophilic drugs through membranes, passive diffusion of hydrophilic drugs through pores, and active transport of larger molecules via transport proteins.

Factors Affecting Drug Absorption

Physiological Factors

Gastrointestinal (GI) anatomy and physiology play a significant role, with the small intestine being the major site for drug absorption in humans.

Gastrointestinal transit times affect absorption rates; for instance, the average intestinal transit time is approximately 3-4 hours, while the large intestine can take 8-72 hours.

Gastric emptying (GE) influences how quickly a drug reaches the small intestine, with factors such as food presence and emotional states affecting GE rates.

Physicochemical Factors

The ionization state of a drug is critical; for example, bases generally have higher intestinal absorption compared to acids and neutrals.

Molecular weight (MW) impacts bioavailability; molecules larger than 400 g/mol typically show reduced absorption.

Lipophilicity, measured by partition coefficients (Log P and Log D), is a key determinant of drug absorption, with optimal values for oral drugs ranging from 1-3 for Log D and 0-3 for Log P.

Drug Stability and Formulation

Stability in the GI Tract

Drugs must withstand harsh biological environments in the GI tract, including extreme pH levels and enzymatic degradation, to be effective.

Drugs like insulin, which are metabolized by GI enzymes, cannot be administered orally and require alternative routes.

Dosage Forms and Their Impact on Absorption

Various dosage forms (tablets, capsules, suspensions) influence absorption rates, with solutions generally being absorbed faster than suspensions or tablets.

Disintegration and dissolution are critical processes; disintegration refers to the breakdown of dosage forms into smaller particles, while dissolution is the rate at which the drug dissolves in gastrointestinal fluids.

Role of Excipients in Drug Formulation

Importance of Excipients

Excipients are inactive substances used in drug formulations to aid in the manufacturing process, enhance stability, and improve absorption.

They serve various functions, such as binders, disintegrants, or pH adjusters, ensuring the proper performance of the dosage form.

Excipients in Drug Formulation

Functions of Excipients

Excipients play a crucial role in drug formulation by ensuring proper dosing, stability, and release of the active ingredient.

They help maintain the integrity of the drug during storage and transport, preventing degradation or loss of potency.

The choice of excipients can influence the drug's bioavailability, affecting how well and how quickly it works in the body.

Proper physicochemical interactions between excipients and active ingredients are essential for optimal therapeutic outcomes.

Examples of excipients include binders, fillers, disintegrants, and lubricants, each serving specific functions in the formulation.

The compatibility of excipients with active ingredients must be assessed to avoid adverse interactions that could compromise drug efficacy.

Types of Specially Formulated Oral Drugs

Enteric Coating: Protects drugs from stomach acidity, allowing them to dissolve in the small intestine.

Sustained Release: Delivers drugs at a controlled rate over an extended period, improving patient compliance and therapeutic effectiveness.

Delayed Release: Allows for the release of the drug after a certain period, which can be beneficial for drugs that require specific timing for absorption.

Examples of Enteric Coating Materials: Include cellulose acetate phthalate (CAP), polyvinyl acetate phthalate (PVAP), and hydroxypropyl methylcellulose phthalate (HPMCP).

Sustained Release Mechanisms: Can involve matrix systems, coating techniques, or granulation methods to achieve desired release profiles.

Clinical Implications: Understanding these formulations is critical for optimizing drug therapy and minimizing side effects.

pH, pKa, and Drug Absorption

Ionization and Drug Absorption

The degree of ionization of a drug affects its lipid solubility and, consequently, its absorption in the body.

pH influences the ionization state of drugs, with weak acids and bases behaving differently based on the surrounding pH.

The Henderson-Hasselbalch equation helps predict the ionization of weak acids and bases:

For weak acids:

pH = pKa + log([A-]/[HA])

For weak bases:

pH = pKa + log([B]/[BH+])

Drugs are more likely to be absorbed when they are in their un-ionized form, which is often more lipid-soluble.

Example: Aspirin (pKa = 4.5) is absorbed in the stomach (pH = 2) due to its un-ionized form predominating.

Understanding these principles is essential for predicting drug behavior in different physiological environments.

pH Partition Theory

The pH partition theory explains how the ionization of drugs affects their distribution across different body compartments.

Acidic drugs tend to concentrate in higher pH environments, while basic drugs concentrate in lower pH environments.

Example: Strychnine (pKa = 9.5) is not absorbed until it reaches the higher pH of the small intestine.

This theory is crucial for understanding the pharmacokinetics of drugs and their therapeutic effects.

Variations in pH across different compartments (e.g., stomach vs. blood) can significantly impact drug absorption and efficacy.

Clinicians must consider these factors when prescribing medications to ensure optimal therapeutic outcomes.

Drug Interactions and Absorption Routes

Drug-Drug Interactions

Drug-drug interactions can alter the pharmacokinetics and pharmacodynamics of co-administered drugs, leading to increased or decreased plasma concentrations.

Pharmacokinetic interactions may involve changes in absorption, distribution, metabolism, or excretion of drugs.

Pharmacodynamic interactions can result in synergistic effects (enhanced activity) or antagonistic effects (decreased activity).

Understanding these interactions is vital for preventing adverse effects and ensuring effective therapy.

Example: The interaction between beta-blockers and asthma medications can exacerbate respiratory conditions.

Clinicians should regularly review patient medications to identify potential interactions.

Absorption via Different Routes

Inhalation: Offers rapid absorption due to a large surface area and lower levels of metabolizing enzymes compared to the gastrointestinal tract.

Sublingual and Buccal: Provide direct access to systemic circulation, bypassing first-pass metabolism, suitable for low to medium molecular weight drugs.

Subcutaneous: Absorption is influenced by drug properties and can vary based on the injection site and technique.

Intramuscular: Rate of absorption is affected by blood flow, muscle activity, and drug characteristics.

Transdermal: Allows for systemic absorption through the skin, with two main pathways: transepidermal and transappendageal.

Each route has unique advantages and limitations that must be considered in drug formulation and administration.

Discussion questions

1/6

What is the distinction between drug absorption and drug bioavailability, and why is this differentiation important in pharmacokinetics?

Difficulty: Easy

2/6

Identify and explain three physiological factors that influence oral drug absorption.

Difficulty: Medium

3/6

Discuss the role of lipophilicity in drug absorption and its implications for drug formulation.

Difficulty: Medium

4/6

How do drug-drug interactions affect systemic drug exposure, and what are the potential consequences?

Difficulty: Hard

5/6

Evaluate the significance of enteric coatings in drug formulations and their impact on drug absorption.

Difficulty: Hard

6/6

Analyze the impact of pH and pKa on drug absorption, particularly in relation to weak acids and bases.

Difficulty: Hard