Exam 2 Flashcards by Kappa Epsilon Pi Chapter

2 - Compartment Model (IV bolus dosing)

Body is represented by 2 ______ compartments (________ and _______)

connected; Central; Peripheral

How well did you know this?

Not at all

Perfectly

2 - Compartment Model (IV bolus dosing)

Elimication occurs from the ________

central compartment (aka plasma)

How well did you know this?

Not at all

Perfectly

2 - Compartment Model (IV bolus dosing)

At t = 0 what does Cp and Ct = ?

Cp (plasma) = 0; Ct (tissue) = 0

How well did you know this?

Not at all

Perfectly

2 - Compartment Model (IV bolus dosing)

How many phases?

How well did you know this?

Not at all

Perfectly

2 - Compartment Model (IV bolus dosing)

What are the phases in this model?

Distribution and Elimination

How well did you know this?

Not at all

Perfectly

2 - Compartment Model (IV bolus dosing)

Rate of Distribution is affected by ___________

alpha and beta

How well did you know this?

Not at all

Perfectly

2 - Compartment Model (IV bolus dosing)

Rate of Elimination is affected by ________

beta ONLY

How well did you know this?

Not at all

Perfectly

2 - Compartment Model (IV bolus dosing)

Definition of Vd(ss)

total mass of drug divided by plasma concentration at steady-state

How well did you know this?

Not at all

Perfectly

2 - Compartment Model (IV bolus dosing)

At steady state, the time derivative for the _______ compartment is _____

tissue; 0

How well did you know this?

Not at all

Perfectly

2 - Compartment Model (IV bolus dosing)

Vp stands for ______

volume of the central (plasma) compartment

How well did you know this?

Not at all

Perfectly

2 - Compartment Model (IV bolus dosing)

Vp is also known as ______ (which stands for…)

Vi — initial volume of distribution

How well did you know this?

Not at all

Perfectly

2 - Compartment Model (IV bolus dosing)

Cpo = ____ + _____

A + B

How well did you know this?

Not at all

Perfectly

2 - Compartment Model (IV bolus dosing)

Vp (aka Vi) = ?

= D(o)/Cp(o)
or
= D(o) / A + B

How well did you know this?

Not at all

Perfectly

What is Vd(exp) used for?

for estimating drug in the body during the elimination phase

How well did you know this?

Not at all

Perfectly

Vd(ss) is used for describing _________ on distribution

protein binding effects

How well did you know this?

Not at all

Perfectly

Vd(area) is most closely related to _______ based on _____

overall CL; AUC

so Vd(area) is basically clearance….

How well did you know this?

Not at all

Perfectly

2 - Compartment Model (IV bolus dosing)

Terminal 1/2 life eqn?

t(1/2) = 0.693/(Beta)

How well did you know this?

Not at all

Perfectly

What happens to ____ when F is increased? (Oral Dosing)

Cmax

increase!

How well did you know this?

Not at all

Perfectly

What happens to ____ when F is increased? (Oral Dosing)

T max

no change

How well did you know this?

Not at all

Perfectly

What happens to ____ when F is increased? (Oral Dosing)

AUC

increase!

How well did you know this?

Not at all

Perfectly

What happens to ____ when F is increased? (Oral Dosing)

t(1/2)

no change

How well did you know this?

Not at all

Perfectly

What happens to ____ when CL is increased? (Oral Dosing)

Cmax

decreased

How well did you know this?

Not at all

Perfectly

What happens to ____ when CL is increased? (Oral Dosing)

t(1/2)

decreased

How well did you know this?

Not at all

Perfectly

What happens to ____ when CL is increased? (Oral Dosing)

AUC

Decreased

How well did you know this?

Not at all

Perfectly

What happens to ____ when CL is increased? (Oral Dosing) | Tmax

decreased

What happens to _____ when Vd increases? (Oral Dosing) | Cmax

decreases

What happens to _____ when Vd increases? (Oral Dosing) | Tmax

increases

What happens to _____ when Vd increases? (Oral Dosing) | AUC

no change

What happens to _____ when Vd increases? (Oral Dosing) | t(1/2)

increases

Infusion rate is a (zero or first) order process

zero!! is happening at a constant rate (independent of drug concentration)

Elimination Rate is a (zero or first) order process

1st oder process (Directly proportional to drug concentration)

how to calculate time to steady state

5 t(1/2) (aka 5 half-lives)

4 steps for making IV bolus regimen design

1 - find max maintenance dose 2 - find max dosing interval 3 - find maintenance dose for common dosing interval 4 - re-calculate predicted Cmax(ss) and Cmin(ss) [too see if appropiate]

Ratio of Tau/t(1/2): the ______ the ratio the greater the accumulation

lower

what are the two primary pathways for biologics to be absorbed?

- convective (pore) transport via lymphatic vessels (if > 19 kDa) - diffusion across blood vessels (if less than 16 kDa)

Biologics have a ______ permeability due to _____ molecular weight

low; high

Biologics are administered by ______ route

parenteral

Bioavailability for biologics can be increased by having it interact with ___________ because it causes prevention of _________

FcRn (neonatal Fc receptor); lysosomal degradation

Volume of distribution is generally (low/high) for biologics because of ______

LOW; large size/high molecular weight

T or F: biologics are typically not subjected to metabolism of P450-CYP enzymes

TRUE

2 main ways biologics get eliminated

catabolism; excretion

Biologics can have a longer half life by affinity to FcRn and _______

degree of humanization

Humanization of Biologics: | order the t(1/2) of the types of mAbs from shortest to longest

(shortest) Murine --> Chimeric --> Humanized --> human (longest)

T or F: SC administration of biologics induces less antibody formation than IV administration

FALSE - MORE antibody is made via SC (bc its gotta go through lymphatic system/immune cells)

Covalent linkage of biologics to _______ will improve drug solubility and decrease immunogenicity

Polymer (like PEG)

Polymers attached to biologics will _______ drug solubility and ______ immunogenicity

increase; decrease

what 2 factors can INCREASE the clearance of biologics

Inflammation and Diabetes

Explain immunogenicity (related to biologics) and its effect on efficacy

ADAs are made (anti-drug antibodies); this is strongly associated with diminished efficacy (because the drug is not available to work in the body when bound to an ADA)

Non-Compartmental: | Treat Cp vs t data as _______ distribution

statistical

Non-Compartmental PK aka _________ theory

Statistical Moment

Non-Compartmental: | Uses _________ as an alternative to ____/____

MRT (mean residence time); Ke/t(1/2)

Non-Compartmental: | What does Second moment mean

standard deviation

Non-Compartmental: | what does first moment mean

mean

MRT calculation

= AUMC/AUC or = 1/k(e)

What is MAT and how do you calculate it

MAT = mean absorption time MRT(po) - MRT(IV) aka difference b/w the MRTs of an oral dose and an IV dose

what is MDT and how do you calculate it

``` MDT = mean dissolution time MDT = MRT(po,tab) - MRT(po,soln) ``` mean difference in b/w a solution and tablet (all given orally)

Non-Compartmental:(!!!!) | How to calculate CL

CL = Dose/ AUC (0 --> infinity)

Non-Compartmental: | How to find volume (and its symbol)

V(ss) = CL x MRT (V(ss)) is what is used in NON-compartmental

Benchmark Volumes: | Blood Volume: _____

0.07 L/kg

Benchmark Volumes: | Total Body Water: ______

0.60 L/kg

Benchmark Volumes: | Body volume: ______

1.0 L/kg

``` Benchmark Volumes: Tissue Volume (aqueous): ______ ```

0.53 L/kg

what is Total Body water?

sum of intracellular and extracellular water

Vd value reflects: - ______ of the drug - binding to ______ proteins - binding to _______ proteins

polarity; plasma; tissue

if a drug has a V(d) ~ Total body water: how do you know that a drug is highly bound in BOTH tissues and plasma

f(ub) and f(ut) are small (<0.05) | if Vd is about total body - the ratio of f(ub)/f(ut) =~ 1

what is considered a Large Vd

> 4 L/kg

what is considered a small Vd

~ 0.06 L/kg