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What factors are considered when assessing the absorption of drugs administered orally?
What factors are considered when assessing the absorption of drugs administered orally?
What is indicated for the administration timing of certain medications?
What is indicated for the administration timing of certain medications?
Which statement about drug absorption kinetics is correct?
Which statement about drug absorption kinetics is correct?
How can one differentiate between absolute and relative bioavailability?
How can one differentiate between absolute and relative bioavailability?
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What does absorption kinetics primarily influence in pharmacokinetics?
What does absorption kinetics primarily influence in pharmacokinetics?
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What happens to Cmax when the absorption rate constant (ka) decreases?
What happens to Cmax when the absorption rate constant (ka) decreases?
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How does a decrease in ka affect the time to reach maximum concentration (tmax)?
How does a decrease in ka affect the time to reach maximum concentration (tmax)?
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What impact does a lower ka have on the absorption of a drug over time?
What impact does a lower ka have on the absorption of a drug over time?
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Which of the following best describes the relationship between rate of elimination and ka?
Which of the following best describes the relationship between rate of elimination and ka?
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What does the term 'flip-flop kinetics' imply in the context of pharmacokinetics?
What does the term 'flip-flop kinetics' imply in the context of pharmacokinetics?
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What happens to the Cmax when the ka decreases from 0.8 hr-1 to 0.5 hr-1?
What happens to the Cmax when the ka decreases from 0.8 hr-1 to 0.5 hr-1?
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What is the half-life (t1/2) for both simulations A and B?
What is the half-life (t1/2) for both simulations A and B?
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What is the value of the clearance (CL) for both doses in the simulations?
What is the value of the clearance (CL) for both doses in the simulations?
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Which factor remains unchanged between simulations A and B?
Which factor remains unchanged between simulations A and B?
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What is the relationship of ka to the elimination rate and its impact on tmax?
What is the relationship of ka to the elimination rate and its impact on tmax?
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Regarding the terminal elimination rate constant (k), which statement is accurate?
Regarding the terminal elimination rate constant (k), which statement is accurate?
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What can be inferred about the absorption kinetics if elimination is not rate limiting?
What can be inferred about the absorption kinetics if elimination is not rate limiting?
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What happens to Cmax when absorption rate (ka) decreases?
What happens to Cmax when absorption rate (ka) decreases?
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How does a decrease in clearance (CL) affect tmax?
How does a decrease in clearance (CL) affect tmax?
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Which parameter maintains its value while Cmax increases due to a decrease in clearance?
Which parameter maintains its value while Cmax increases due to a decrease in clearance?
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In scenario B, what is the effect of a higher ka on tmax?
In scenario B, what is the effect of a higher ka on tmax?
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What effect does an increased terminal half-life imply about the drug's elimination?
What effect does an increased terminal half-life imply about the drug's elimination?
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If the absorption kinetics show ka < k, what can be inferred about the drug's behavior?
If the absorption kinetics show ka < k, what can be inferred about the drug's behavior?
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In which scenario would a drug's AUC (Area Under the Curve) remain constant despite changes in kinetics?
In which scenario would a drug's AUC (Area Under the Curve) remain constant despite changes in kinetics?
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What is indicated by a decrease in the slope of the line representing k in elimination kinetics?
What is indicated by a decrease in the slope of the line representing k in elimination kinetics?
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In pharmacokinetics, what does an increase in A (amount of drug in the body) imply if half-life is unchanged?
In pharmacokinetics, what does an increase in A (amount of drug in the body) imply if half-life is unchanged?
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If the elimination half-life is shorter than the terminal half-life, what can be inferred?
If the elimination half-life is shorter than the terminal half-life, what can be inferred?
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What represents the first-order elimination rate constant?
What represents the first-order elimination rate constant?
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If ka >> k, what significantly limits the decline in the plasma concentration due to elimination?
If ka >> k, what significantly limits the decline in the plasma concentration due to elimination?
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Which equation is used to calculate the elimination half-life ($t_{1/2}$)?
Which equation is used to calculate the elimination half-life ($t_{1/2}$)?
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In the presence of a higher absorption rate, which slope is typically observed?
In the presence of a higher absorption rate, which slope is typically observed?
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What factor influences the residual concentration graphically represented in pharmacokinetics?
What factor influences the residual concentration graphically represented in pharmacokinetics?
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What is suggested when the absorption half-life ($t_{1/2,a}$) is longer than the elimination half-life ($t_{1/2}$)?
What is suggested when the absorption half-life ($t_{1/2,a}$) is longer than the elimination half-life ($t_{1/2}$)?
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What does a slope of -ka typically correlate with in pharmacokinetics?
What does a slope of -ka typically correlate with in pharmacokinetics?
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If you retrieve the values C1 and C2 from a graph, what should you remember to do with those values before calculating the elimination rate constant ($k$)?
If you retrieve the values C1 and C2 from a graph, what should you remember to do with those values before calculating the elimination rate constant ($k$)?
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Which equation is used to relate plasma concentration to time for first-order elimination under conditions of constant volume of distribution?
Which equation is used to relate plasma concentration to time for first-order elimination under conditions of constant volume of distribution?
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What occurs to the plasma concentration when both ka and k are positive but ka < k?
What occurs to the plasma concentration when both ka and k are positive but ka < k?
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Which statement correctly describes the relationship between ka and k when absorption rate limits the decline in plasma concentration?
Which statement correctly describes the relationship between ka and k when absorption rate limits the decline in plasma concentration?
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Which term best describes the state when k >> ka?
Which term best describes the state when k >> ka?
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What factor primarily determines the time required for absorption to complete?
What factor primarily determines the time required for absorption to complete?
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In a semi-log plot for drug elimination, what is typically reflected in the terminal slope?
In a semi-log plot for drug elimination, what is typically reflected in the terminal slope?
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What happens to the elimination rate when the volume of distribution (V) decreases?
What happens to the elimination rate when the volume of distribution (V) decreases?
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What effect does a decrease in volume (V) have on tmax?
What effect does a decrease in volume (V) have on tmax?
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In the scenario where volume decreases, how is the amount of drug remaining at the absorption site affected?
In the scenario where volume decreases, how is the amount of drug remaining at the absorption site affected?
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What is the relationship between absorption rate (ka) and the amount absorbed (A) at tmax?
What is the relationship between absorption rate (ka) and the amount absorbed (A) at tmax?
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Which statement best describes control changes observed in pharmacokinetics when V decreases?
Which statement best describes control changes observed in pharmacokinetics when V decreases?
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When the volume of distribution is halved, what happens to the concentration of the drug (C)?
When the volume of distribution is halved, what happens to the concentration of the drug (C)?
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What is a consequence of a net effect when both V and Aa decrease?
What is a consequence of a net effect when both V and Aa decrease?
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At tmax, what equation describes the relationship between the absorption and clearance rates?
At tmax, what equation describes the relationship between the absorption and clearance rates?
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Study Notes
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
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Part 1: Focuses on factors affecting absorption of drugs.
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Factors include oral, IM, and SC administration methods
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Details the types of kinetics involved in drug absorption.
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Expands on how drug concentration changes over time after a single dose (disposition).
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Identifies PK parameters that can be derived from drug profiles.
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Part 2: Focuses on factors influencing the absorption of solid dosage forms in the GI tract.
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Details include what affects the absorption on solid dosages forms in the Gl tract.
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Explores whether terminal slopes in EV dose profiles are consistently representative of elimination rate constants.
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Explains how absolute versus relative bioavailability is determined.
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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).
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Description
This quiz covers the pharmacokinetics concepts related to drug absorption in the gastrointestinal system. It discusses the impact of food on medication intake, various administration methods, and the kinetics of absorption. Learn about how different factors influence the absorption rates of drugs administered orally, intramuscularly, and subcutaneously, as well as the PK parameters that can be derived from absorption profiles.
