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Kinetics PHRM 846 > Exam 2 > Flashcards

Exam 2 Flashcards

1
Q

2 - Compartment Model (IV bolus dosing)

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

A

connected; Central; Peripheral

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2
Q

2 - Compartment Model (IV bolus dosing)

Elimication occurs from the ________

A

central compartment (aka plasma)

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3
Q

2 - Compartment Model (IV bolus dosing)

At t = 0 what does Cp and Ct = ?

A

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

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4
Q

2 - Compartment Model (IV bolus dosing)

How many phases?

A

2

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5
Q

2 - Compartment Model (IV bolus dosing)

What are the phases in this model?

A

Distribution and Elimination

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6
Q

2 - Compartment Model (IV bolus dosing)

Rate of Distribution is affected by ___________

A

alpha and beta

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7
Q

2 - Compartment Model (IV bolus dosing)

Rate of Elimination is affected by ________

A

beta ONLY

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8
Q

2 - Compartment Model (IV bolus dosing)

Definition of Vd(ss)

A

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

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9
Q

2 - Compartment Model (IV bolus dosing)

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

A

tissue; 0

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10
Q

2 - Compartment Model (IV bolus dosing)

Vp stands for ______

A

volume of the central (plasma) compartment

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11
Q

2 - Compartment Model (IV bolus dosing)

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

A

Vi — initial volume of distribution

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12
Q

2 - Compartment Model (IV bolus dosing)

Cpo = ____ + _____

A

A + B

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13
Q

2 - Compartment Model (IV bolus dosing)

Vp (aka Vi) = ?

A

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

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14
Q

What is Vd(exp) used for?

A

for estimating drug in the body during the elimination phase

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15
Q

Vd(ss) is used for describing _________ on distribution

A

protein binding effects

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16
Q

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

A

overall CL; AUC

so Vd(area) is basically clearance….

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17
Q

2 - Compartment Model (IV bolus dosing)

Terminal 1/2 life eqn?

A

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

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18
Q

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

Cmax

A

increase!

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19
Q

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

T max

A

no change

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20
Q

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

AUC

A

increase!

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21
Q

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

t(1/2)

A

no change

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22
Q

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

Cmax

A

decreased

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23
Q

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

t(1/2)

A

decreased

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24
Q

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

AUC

A

Decreased

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25
Q

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

Tmax

A

decreased

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26
Q

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

Cmax

A

decreases

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27
Q

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

Tmax

A

increases

28
Q

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

AUC

A

no change

29
Q

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

t(1/2)

A

increases

30
Q

Infusion rate is a (zero or first) order process

A

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

31
Q

Elimination Rate is a (zero or first) order process

A

1st oder process (Directly proportional to drug concentration)

32
Q

how to calculate time to steady state

A

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

33
Q

4 steps for making IV bolus regimen design

A

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]

34
Q

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

A

lower

35
Q

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

A
  • convective (pore) transport via lymphatic vessels (if > 19 kDa)
  • diffusion across blood vessels (if less than 16 kDa)
36
Q

Biologics have a ______ permeability due to _____ molecular weight

A

low; high

37
Q

Biologics are administered by ______ route

A

parenteral

38
Q

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

A

FcRn (neonatal Fc receptor); lysosomal degradation

39
Q

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

A

LOW; large size/high molecular weight

40
Q

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

A

TRUE

41
Q

2 main ways biologics get eliminated

A

catabolism; excretion

42
Q

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

A

degree of humanization

43
Q

Humanization of Biologics:

order the t(1/2) of the types of mAbs from shortest to longest

A

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

44
Q

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

A

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

45
Q

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

A

Polymer (like PEG)

46
Q

Polymers attached to biologics will _______ drug solubility and ______ immunogenicity

A

increase; decrease

47
Q

what 2 factors can INCREASE the clearance of biologics

A

Inflammation and Diabetes

48
Q

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

A

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)

49
Q

Non-Compartmental:

Treat Cp vs t data as _______ distribution

A

statistical

50
Q

Non-Compartmental PK aka _________ theory

A

Statistical Moment

51
Q

Non-Compartmental:

Uses _________ as an alternative to ____/____

A

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

52
Q

Non-Compartmental:

What does Second moment mean

A

standard deviation

53
Q

Non-Compartmental:

what does first moment mean

A

mean

54
Q

MRT calculation

A

= AUMC/AUC

or
= 1/k(e)

55
Q

What is MAT and how do you calculate it

A

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

56
Q

what is MDT and how do you calculate it

A 
MDT = mean dissolution time
MDT = MRT(po,tab) - MRT(po,soln)

mean difference in b/w a solution and tablet (all given orally)

57
Q

Non-Compartmental:(!!!!)

How to calculate CL

A

CL = Dose/ AUC (0 –> infinity)

58
Q

Non-Compartmental:

How to find volume (and its symbol)

A

V(ss) = CL x MRT

(V(ss)) is what is used in NON-compartmental

59
Q

Benchmark Volumes:

Blood Volume: _____

A

0.07 L/kg

60
Q

Benchmark Volumes:

Total Body Water: ______

A

0.60 L/kg

61
Q

Benchmark Volumes:

Body volume: ______

A

1.0 L/kg

62
Q 
Benchmark Volumes: 
Tissue Volume (aqueous): \_\_\_\_\_\_
A

0.53 L/kg

63
Q

what is Total Body water?

A

sum of intracellular and extracellular water

64
Q

Vd value reflects:

  • ______ of the drug
  • binding to ______ proteins
  • binding to _______ proteins
A

polarity; plasma; tissue

65
Q

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

A

f(ub) and f(ut) are small (<0.05)

if Vd is about total body - the ratio of f(ub)/f(ut) =~ 1

66
Q

what is considered a Large Vd

A

> 4 L/kg

67
Q

what is considered a small Vd

A

~ 0.06 L/kg

Kinetics PHRM 846 (2 decks)

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