Pharmacokinetics Overview

Questions and Answers

What does the term AUC represent in pharmacokinetics?

Absorption under the concentration

Average unit clearance

Available uptake concentration

Area under the curve (correct)

How is drug clearance generally calculated in clinical practice?

Elimination constant divided by volume of distribution

Plasma drug concentration subtracted from dose

Dose divided by the AUC (correct)

Volume of distribution multiplied by half-life

When is the clearance of a drug typically estimated from a plasma drug concentration (Css)?

During a continuous infusion at steady state (correct)

After a single intravenous dose

When the drug is administered orally

Only at the time of peak concentration

What does a high elimination constant (K) indicate about the drug's half-life?

The plasma concentration decreases rapidly Signup and view all the answers

In pharmacokinetics, what is the relationship between volume of distribution (V) and initial concentration?

Higher V leads to lower initial concentration Signup and view all the answers

What is a defining feature of drugs with linear pharmacokinetics?

Rate of change in drug concentration is constant Signup and view all the answers

What does the term clearance in pharmacokinetics best represent?

The elimination of drugs from the body Signup and view all the answers

Why is pharmacokinetic analysis beneficial when using mathematical models?

It simplifies dosing and therapeutic decisions Signup and view all the answers

What remains constant regardless of drug concentration?

The half-life of the drug Signup and view all the answers

What does the AUC represent in pharmacokinetics?

Total drug exposure over time Signup and view all the answers

Which pharmacokinetic model assumes instantaneous distribution of the drug?

Simple linear model Signup and view all the answers

What happens to the AUC if the infusion duration is shortened?

AUC increases due to slower clearance Signup and view all the answers

What must be precisely timed to ensure the validity of pharmacokinetic modeling?

Drug infusions Signup and view all the answers

What is likely to happen when a drug exhibits nonlinear pharmacokinetic behavior?

The AUC increases disproportionately with higher doses Signup and view all the answers

Which of the following drugs has been shown to have nonlinear pharmacokinetics?

Cisplatin Signup and view all the answers

What is meant by a drug's bioavailability?

Proportion of administered dose reaching systemic circulation Signup and view all the answers

Which factor is NOT a common reason for interpatient variability in pharmacokinetics?

Consistency in drug dosing Signup and view all the answers

Which example of drug is influenced by saturable absorption processes?

Methotrexate Signup and view all the answers

When comparing two pharmacokinetic models, what is important to ensure?

Use of non-compartmental and specific model results Signup and view all the answers

How can the AUC for a 90 mg/m2 dose be estimated from a 60 mg/m2 dose?

It can be estimated as being 50% greater Signup and view all the answers

How does the AUC behave when the dose of 5-FU is doubled from 7.5 mg/kg to 15 mg/kg?

Increases by 135% Signup and view all the answers

What primarily limits the bioavailability of (6R) leucovorin?

Absorption issues Signup and view all the answers

How may concomitant administration of certain chemotherapeutic agents affect drug bioavailability?

It may decrease bioavailability through gastrointestinal toxicity Signup and view all the answers

What factor can lead to altered distribution of lipophilic drugs in patients?

Changes in body size or fat ratio Signup and view all the answers

What is particularly significant about the elimination of methotrexate?

It accumulates in body fluids leading to delayed clearance Signup and view all the answers

What could potentially increase a patient's risk of toxicity related to chemotherapy?

Low serum albumin concentration Signup and view all the answers

Why is understanding hepatic elimination important in chemotherapy dosing?

Many anticancer agents are metabolized or excreted by the liver Signup and view all the answers

What is indicated when renal function changes in a patient undergoing chemotherapy?

Importance of modifying drug doses based on clearance Signup and view all the answers

What is a well-established relationship in individual drug dosing?

Hepatic function correlates with drug clearance Signup and view all the answers

What variability factor has been well-studied for the drug 5-FU?

Circadian rhythm affecting plasma concentrations Signup and view all the answers

What happens to the clearance of paclitaxel when administered after cisplatin?

It is decreased when given second Signup and view all the answers

Which factor affects the clearance of topotecan during moderate renal dysfunction?

Requirement for dose reduction Signup and view all the answers

What impact does cumulative dosing have on patient sensitivity to chemotherapy?

Increased sensitivity to subsequent doses may occur Signup and view all the answers

What might result from changes in hepatic or renal function over time during chemotherapy?

Increased toxicity due to altered drug exposure Signup and view all the answers

Which drug is known for significant intrapatient pharmacokinetic variability due to circadian rhythm?

5-FU Signup and view all the answers

Study Notes

Understanding Federal Websites

Federal government websites typically end with .gov or .mil, indicating they are official sites.
Ensure the connection is secure by looking for https://, which ensures encryption of sensitive information.

Overview of Pharmacokinetics

Pharmacokinetics examines drug absorption, distribution, metabolism, and excretion.
Drug clearance refers to the elimination of drugs from the body, analogous to creatinine clearance.

Key Concepts in Pharmacokinetics

Clearance is calculated using the AUC (area under the curve); a higher AUC for a given dose results in lower clearance.
Continuous infusion reaches steady state, allowing clearance estimation from a single plasma drug concentration measurement.

Pharmacokinetic Models

Basic pharmacokinetic equations include variables for volume of distribution (V) and elimination constant (K).
V represents the volume where the drug dose is diluted; higher V results in lower initial concentration.
K is inversely proportional to half-life: shorter half-life means a higher K and rapid plasma concentration decline.

Linear Pharmacokinetics

In linear pharmacokinetics, the rate of change in drug concentration is dependent on current concentration.
Half-life remains constant regardless of concentration, impacting drug exposure calculations like AUC.
AUC is proportional to the dose: an increase in dose can predictably increase the AUC.

Nonlinear Pharmacokinetics

Nonlinear behavior arises when metabolic pathways become saturated, leading to decreased clearance and increased AUC at higher doses.
Examples include 5-FU and paclitaxel, where shorter infusion times resulted in higher AUC without increased toxicity.

Factors Influencing Bioavailability

Bioavailability is the percentage of a drug absorbed; it is calculated by comparing AUCs from oral versus intravenous administration.
Factors affecting bioavailability include drug metabolism in the gastrointestinal tract and liver.

Variability in Pharmacokinetics

Interpatient variability can significantly influence pharmacokinetic parameters, exacerbated by hepatic or renal dysfunction.
Genetic differences in metabolism can lead to variability in drug response; pharmacogenetic variations are crucial for therapeutic optimization.

Impacts of Physiological Abnormalities

Abnormal drug distribution often occurs due to factors like body size or fat ratio.
Hepatic function impacts drug metabolism; lower serum albumin levels may result in increased risk for toxicity.

Renal Function and Drug Clearance

Renal function directly correlates with drug clearance; conditions like ureteral obstruction or volume depletion can alter renal function and drug exposure.
Drugs like carboplatin require careful renal function assessment for appropriate dosing.

Circadian Variability

Intrapatient pharmacokinetic variability may occur, influenced by circadian rhythms; drugs like 5-FU have shown significant concentration variability based on administration timing.

Combination Chemotherapy Considerations

Cancer treatments often involve combination therapies, where drugs like paclitaxel and cisplatin may interact, impacting clearance rates.
Inhibitors such as cyclosporin A can unexpectedly affect drug clearance, highlighting the importance of monitoring responses.

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Description

This quiz covers the basics of pharmacokinetics, focusing on drug absorption and the importance of recognizing secure federal websites. It emphasizes the significance of understanding drug delivery systems and the protocols for sharing sensitive information online. Test your knowledge on these vital topics!