Pharmaceutics II Exam 4

Describes the efficiency of drug elimination from the body. It is defined as the hypothetical volume of plasma from which a drug is completely and irreversibly removed per unit of time (e.g., L/h or mL/min)

Clearance

This is the sum of all individual organ clearances (e.g., renal, hepatic)

Total body clearance

Along with the volume of distribution, this is a primary pharmacokinetic parameter that reflects fundamental biochemical and physiological processes

Clearance

If you know the elimination rate constant (k) and the volume of distribution (Vd), you can find the ________

Clearance

For a fixed Vd, a decrease in clearance leads to a _______ in k, which in turn increases the half-life

Decrease

For a given dose, the overall drug exposure (AUC) is inversely proportional to ________

Clearance

If clearance goes down (due to organ impairment), the drug stays in the body longer, and exposure (AUC) goes ___

Up

Rate of blood entering the organ

Q

The fraction of drug entering the organ that is cleared

E

Individual organ clearance can never exceed the _______ ______ rate to that organ

Blood flow

The volume of plasma cleared of a drug by the kidneys per unit of time; involves filtration, secretion, and reabsorption

Renal clearance

Passive process; limited to unbound (free) drug and small molecules (<70 kD)

Filtration

Active process; uses carriers; can be saturated; not affected by protein binding

Secretion

Passive process; dependent on urine pH and drug ionization

Reabsorption

What is the normal glomerular filtration rate?

120 mL/min

When renal clearance > GFR, active _________ is occurring

Secretion

When renal clearance < GFR, passive _________ is occurring or the drug is highly protein-bound

Reabsorption

Used as a biomarker for renal function (estimating GFR) because it has minimal protein binding, secretion, or reabsorption

Creatinine

For weak bases, _______ urine increases ionization, which prevents reabsorption and increases clearance

Acidic

For weak acids, _______ urine will increase clearance

Basic

Large drugs (like monoclonal antibodies >70 kD) have low renal clearance because they are too big to be _______ by the glomerulus

Filtered

If a patient has kidney injury, their renal clearance decreases. This results in a _______ k, an increased half-life, and an increased AUC; requires a dose decrease

Decreased

One-compartment assumption is instantaneous and rapid _________

Distribution

Two-compartment assumption is distribution to some tissues is ____

Slow

Two-compartment model; highly perfused tissues like the blood, heart, liver, and kidneys; distribution here is rapid

Central compartment

Two-compartment model; tissues with lower perfusion or higher drug affinity, such as fat, muscle, and cerebrospinal fluid; distribution here is slow

Peripheral compartment

Represents transfer rate from central to peripheral compartment

k12

Represents transfer rate from peripheral back to central compartment

k21

Represents elimination rate constant (drug is only eliminated from the central compartment)

k10

Represents the initial fast decline in plasma concentration

Alpha

Represents the slower, terminal decline after equilibrium is reached

Beta

Alpha is always ______ than beta; the alpha term approaches zero quickly, while the beta term dominates at later time points

Alpha

Represents the total drug exposure over time

AUC

You must wait until _________ equilibrium before taking a plasma sample in two-compartment system to ensure the Cp accurately reflects drug levels in all tissues

Distribution

A large ________ _______ can cause toxicity because of the initial high concentration in the central compartment before it has time to distribute to other tissues

Loading dose

Provides immediate delivery of the full dose, resulting in the highest concentration and most rapid effect. However, it cannot maintain a steady concentration and dosing errors can be dangerous

IV Bolus

Provides slow, sustained delivery. It allows for precisely controlled administration and maintains constant plasma levels over long periods while minimizing fluctuations

IV Infusion

In IV infusion, the drug enters the body at a ________ rate (Q) - zero-order input

Constant

In IV infusion, the drug leaves the body at a rate ________ to its concentration (first-order elimination)

Proportional

Occurs when the rate of drug intake equals the rate of drug elimination (input = output)

Steady state

Theoretically, it takes an infinite amount of time to reach 100% steady-state

True steady-state

Defined as reaching 95% of the steady-state concentration

Practical steady-state

The time to reach steady-state is ________ of the infusion rate (Q); depends only on the drug’s half-life

Independent

It takes approximately _____ half-lives to reach practical steady-state

4.32

The concentration at steady-state is directly proportional to the _________ rate

Infusion

If a drug has a long half-life, it takes too long to reach steady-state concentration; a ______ _____ is used to reach the desired concentration instantly

Loading dose

Once the infusion stops, the drug clears the body following ____-order elimination, just like an IV bolus

First

Increasing infusion rate _______ concentration at steady state

Increases

Increasing half-life __________ concentration at steady-state

Increases

Increasing clearance _________ concentration at steady state

Decreases

Increasing half-life _______ time to reach steady-state

Increases

Increasing clearance _______ time to reach steady-state

Decreases

At steady-state, the elimination rate is exactly _____ to the infusion rate

Equal

If you have the infusion rate (Q) and the steady-state concentration, you can always find _________

Clearance

The infusion process is _____-order (constant rate)

Zero

The elimination process is typically _____-order

First

Describes how a drug enters and leaves the body after being swallowed; unlike an IV bolus, it has an absorption phase

Oral dosing

Oral dosing usually follows a ____-compartment model

One

In oral dosing, both absorption and elimination typically follow ____-order kinetics

First

Absorption rate constant

ka

Elimination rate constant

k

Typically ka is ______ than k (the drug absorbs faster than it is eliminated)

Greater

The rate of drug entering the body is higher than the rate leaving (kaDa > kD)

Absorption phase

Rate of absorption equals the rate of elimination (dD/dt = 0)

tmax

Most of the drug has been absorbed, so the rate of drug leaving exceeds the rate entering (kaDa < kD)

Elimination phase

Oral dosing, is tmax dose dependent?

No

Oral dosing, is Cmax dose dependent?

Yes

Oral dosing; is AUC dose dependent?

Yes

If ka increases, tmax ________ (reaches peak faster)

Decreases

If you double the dose, Cmax _______

doubles

The fraction of the dose that actually reaches the systemic circulation

F

Compares the oral dose to an IV bolus (the “gold standard” where F = 100%)

Absolute bioavailability

Compares two different non-IV dosage forms (e.g., tablet vs. solution)

Relative bioavailability

If you are switching a patient from an IV to oral, the oral dose must be ________ to achieve the same AUC

Higher

Predicts absorption based on solubility and permeability

BCS

High solubility and high permeability

Class 1

Low solubility and high permeability

Class 2

High solubility and low permeability

Class 3

Low solubility and low permeability

Class 4

For a generic drug to be approved, it must be ________ _______ to the brand name (RLD)

Therapeutically equivalent

Same API, same strength, and same dosage form

Pharmaceutical equivalence

Statistically equivalent Cmax and AUC

Bioequivalence

The difference between the test and reference product for Cmax and AUC should be less than _____ to be bioequivalent

20%

Generics use an ________, which requires bioequivalence studies but not new clinical safety/efficacy trials

ANDA

The FDA’s official list of approved drug products with therapeutic equivalence evaluations

Orange Book

Designed to maintain prolonged therapeutic activity by giving doses at repeating intervals

Multiple dosage regimen

What parameters do not change with the number of doses in multiple dosage regimen?

k, Vd, Cl

Occurs when the amount of drug eliminated during one dosing interval equals the dose administered; input=output

Steady-state

Cssmax increases if dose _______ or T _________

Increases or decreases

Cssavg is determined by the _______ _______

Dosing rate

Cssavg is not the arithmetic average of Cmax and Cmin because drug elimination is ________, not linear

Exponential

Measures the “swing” between peak and trough

Fluctuation factor

Fluctuation factor depends solely on the ______ ________ (and the patient’s k)

Dosing interval

As dosing interval (T) increases, fluctuation _______

Increases

Compares steady-state concentrations to the first dose

Accumulation factor

If you increase the dosing interval (T), accumulation factor ________ because there is more time for the drug to be removed

Decreases

Oral Cssmax is always ______ than IV

Lower

Oral Cssmin is always _______ than IV

Higher

Fluctuation is always ______ for oral dosing because the absorption phase “smooths” the curve

Lower

Used to achieve steady-state concentrations instantaneously

Loading dose