Gastrointestinal System Absorption Quiz

Gastrointestinal System Absorption

• The presentation covers PK concepts for absorption.
• It discusses the importance of considering food when taking medication.
• There are different ways for taking medication: with or after food, before food.
• Factors affecting absorption of drugs include those administered orally, IM, and SC.
• Drug absorption kinetics follow certain types of kinetics.
• Absorption rates change over time after a single dose.
• PK parameters derived from profiles following single EV doses.

Overview of Absorption Lectures

• Part 1: Focuses on factors affecting absorption of drugs.

• Factors include oral, IM, and SC administration methods

• Details the types of kinetics involved in drug absorption.

• Expands on how drug concentration changes over time after a single dose (disposition).

• Identifies PK parameters that can be derived from drug profiles.

• Part 2: Focuses on factors influencing the absorption of solid dosage forms in the GI tract.

• Details include what affects the absorption on solid dosages forms in the Gl tract.

• Explores whether terminal slopes in EV dose profiles are consistently representative of elimination rate constants.

• Explains how absolute versus relative bioavailability is determined.

• Discusses the influence of changes in absorption kinetics and disposition kinetics on PK parameters.

Absorption Part 2 Learning Outcomes

• Students will understand the role of gastric emptying and intestinal transit in drug absorption, considering physicochemical properties of the drug and its dosage form.
• Students will differentiate between dissolution and permeability rate limitations in systemic absorption following oral administration.
• Students will understand the difference between disposition and absorption-rate limited drug elimination.
• Students will be able to recognise flip-flop of two rate constants, k₁ and k, in absorption rate-limited situations.
• Students will learn to calculate absolute and relative bioavailability using plasma concentration data.
• Students will discuss changes in absorption-related PK parameters.

Factors Affecting Solid Dosage Forms Absorption in GI Tract

• Gastric emptying and intestinal transit affect absorption rate.
• Dissolution rate (permeability or solid dissolution) limits the rate of absorption.
• Dissolution, Permeability as rate-limiting step during absorption.
• Factors influencing GI motility will be evaluated.

GI Motility x Rate-Limited Absorption

• Permeability rate-limits absorption.
• Slowing of motility allows more time for absorption, compensating for poor permeability.
• Increased motility can exacerbate permeability issues.
• The drug should be chemically stable during transit in the GI tract.

Factors Affecting GI Motility

• Food intake (volume, type) significantly impacts GI motility.
• Type of food matters.
• Certain drugs, like anticholinergics and opioids, slow motility.
• Prokinetics speed up motility.
• Physiological conditions like pregnancy and illness influence motility.
• Body position also affects motility.

GI Motility x Absorption of Solid Dosage Forms

• Factors affecting GI motility impact gastric emptying rate and intestinal motility.
• This impacts the rate of presentation of a drug to the intestines and how long it resides there for absorption.
• Solubility and membrane permeability are significant factors.

Factors Affecting Absorption in the GI Tract (Summary)

• Physiochemical factors (size, lipophilicity, charge, solubility) and physiological factors (membrane porosity, membrane thickness, transporter involvement, blood flow, total absorptive area, DMF, gastric motility) influence absorption and are crucial to determining the release characteristics of the dosage form.

Clinical Application of PK Concepts

• Recognizing how drugs are affected by food.
• Guidelines on when to take medications with or without food are available.
• Links to resources on drug-food interactions.

When Looking at an EV Dose Profile

• Determine if terminal slope always represents the elimination rate constant.
• Absorption rate versus disposition rates impact interpretation of terminal slope in EV dose profiles.

IV vs EV Exposure Time Profiles

• IV and EV administration impact exposure time profiles.
• Differences in drug profiles may be attributed to absorption vs elimination rates.

PK Parameters (k, t1/2, ka, and t1/2,a)

• First-order elimination rate constant (k).
• Elimination half-life (t1/2).
• First-order absorption rate constant (ka).
• Absorption half-life (t1/2,a).

When k >> ka (Disposition Rate-Limits Decline in PDC)

• Absorption is significantly slower than elimination.
• The terminal slope reflects the elimination rate.

When k << ka (Flip-Flop)

• Absorption rate-limits decline in PDC
• The terminal slope reflects the absorption, not elimination rate.

Distinguishing Between Disposition vs Absorption Rate-Limited Elimination

• Compare EV profiles with IV bolus profiles to determine if elimination.
• Considering different dosage forms (e.g., immediate-release vs extended-release) and terminal half-life change.

Clinical Implications of Flip-Flop Kinetics

• Accurately determining k and ka is essential
• When absorption rate limits disposition, a prolonged half-life can lead to less frequent drug dosing.
• Consider factors like rate of permeability, dissolution, and formulation that may have implications.

Example: Which is Disposition- vs Absorption-Rate Limited Elimination?

• Various examples of drug profiles are presented.
• Examples contrast IV and other methods to understand these distinctions.

How Do We Determine Absolute vs Relative Bioavailability?

• Absolute and relative bioavailability are measured based on study design.
• A standard design that is used to determine absolute vs relative bioavailability is a cross-over study.

Oral Systemic Bioavailability

• The fraction of a drug that reaches the liver after oral administration represents oral systemic bioavailability
• A portion of the drug escapes extraction within the liver.
• Some of the drug is metabolized in the liver and some is eliminated through the Biliary system.

Absolute vs Relative Bioavailability

• Absolute bioavailability assesses the fraction of a drug that reaches systemic circulation, compared to intravenous administration. .
• Relative bioavailability measures the systemic availability comparing drugs, dosage forms or administration routes versus a standard form, typically the IV route.

Study Design of Bioavailability Studies

• Crossover designs commonly used in bioavailability studies.
• Subjects receive different treatments in a defined order.
• Controls for variability between subjects.

Changing Amounts Absorbed, Absorption Kinetics, and Disposition Kinetics

• Changes in the amount absorbed, along with changes in absorption kinetics and disposition kinetics, impact pharmacokinetic (PK) parameters and the overall exposure-time profile (EV profile) impacting the overall exposure-time profile.
• Understanding how these factors impact the EV profile is crucial in designing drug therapies.

Changing Absorption Kinetics

• Changes in the absorption rate constant (ka) impact other PK parameters like Cmax, tmax, AUC0-∞, and terminal half-life.
• Changes in ka have implications on the time it takes to reach maximum concentration and the overall drug exposure.

Changing Disposition Kinetics

• Changes in the clearance (CL) or volume of distribution (V) impact the terminal half-life and overall exposure-time profile.
• Altered disposition kinetics significantly impact drug plasma concentration profiles.

Integration of Kinetics and Physiological Concepts

• Various GI factors, including motility, affect both the rate and extent of absorption.
• Food intake, for example, can alter both rate and extent impacting the drug’s pharmacokinetics profile.

Example: Inhibition of First-Pass Metabolism

• Enzyme inhibition can increase bioavailability (F).
• This can lead to altered parameters such as the maximum concentration (Cmax) and the time to reach maximum concentration (tmax).