Extravascular Dose

Question 1

T or F: when giving IV dose, 90% of it gets to circulation and then elimination starts right away

Answer 1

F - 100% gets to circulation right away and then conc of plasma decreases via elimination right away

** get Cmax right away

elimination - governed by k

extent of drug exposure measured by AUC ( dose/Cl)

Question 2

Different RoA

Answer 2

oral, sublingual, buccal, rectal etc

Question 3

What impacts C plasma

Answer 3

rate and extend of absorption

Question 4

What is bioavailability?

Answer 4

F= measures the fraction of dose that gets to circulation

—- measure of extent of absorption

Question 5

How to measure systemic exposure in extravascular route

Answer 5

AUC = F * Dose/Cl

Question 6

How to get F ?

Answer 6

Absolute F = comparing AUC for Route of interest vs IV

F= AUC po * Dose iv/ AUC iv * Dose oral

• corrects for differences in doses

Question 7

What does the rate of absorption of oral route depend on

Answer 7

conc of drug at absorption sites
- first order dependent
C dependent

Question 8

Conc of drug in plasma if not IV

Answer 8

Co - is 1 and then slowly rises as drug is absorbed (A> E)
- absorption is fastest at start when A is the highest and slows down as it equals 1 (less present)
- eventually evens out as A = E. and then declines as E> A

Question 9

When do you see 0 order kinetics

Answer 9

modified release drugs

Question 10

How to get Rate of absorption

Answer 10

RoA = ka * A (amount at site)

ka and t1/2a are faster when drug already in solution

Question 11

What happens to Cmax and Tmax if extent of absorption decreases

Answer 11

Cmax = decreases
tmax - doesn’t change

Question 13

T or F: Cmax of IV is always greater than Cmax of non-IV

Answer 13

T because in non-IV as drug absorbed —- some also eliminated at same time

—- decrease in Cmax == increase in T max

is ka (rate of A) is slower —- Cmax decreases and Tmax increases

Question 14

T or F: IM is always faster than oral

Answer 14

T- because in solution already === Cmax is higher and tmax is shorter

Question 15

T or F: Cmax is a function of only extent of absorption

Answer 15

F - fxn of rate and extent

Tmax: only dependent on rate (not F/extent)

Question 16

What is onset

Answer 16

related to when drug gets to MEC at site of action (able to have onset of action)
faster A — faster onset — and can sometimes mean more intense effects if Cmax if higher

Question 17

What is duration

Answer 17

time spent above MEC (slower A - may mean stay about MEC for longer)

Question 18

What are the requirements for the method of residuals to work for calculation of Ka

Answer 18

1) ka> k (4-5X)
2) terminal phase must only represent elimination (can confirm if slope of terminal IV and oral == parallel)
—— because K = constant for all RoA

Question 19

What is the flip-flop model

Answer 19

when terminal phase is not only impacted by elimination
- absorption rate dependent /limited

• can see when IV and non-IV lines aren’t parallel in terminal phase

**more common in MR drugs

Question 20

What is absorption lag time drugs

Answer 20

drugs that have a lag before absorption occurs
- causes graph to shift R (tmax increases but Cmax doesnt’ change or AUC)

Question 21

How to get absolute F

Answer 21

use crossover study: look at Ae for IV and other RoA and compare
- need to ensure Cl not impacting Ae

Question 22

What are the worries with low absolute F

Answer 22

• Gi toxicity (shift left, more chilling in GI )
• variability (as F decreases - more variability in how people are impacted by doses )

Question 23

Relative F

Answer 23

not compare IV and non-IV
- compare two different DF of same product or generics

Question 24

what is a pharmaceutical equivalent

Answer 24

generic - same AI, same RoA, strength, DR, conditions of use

Question 25

Bio equivalents

Answer 25

same rate and extent of absorption - therapeutic equivalents if bioequivlaence and pharmaceutical equivalence are the same

Question 26

Bio equivalence Study Criteria

Answer 26

appropriate sampling times to get Cmax and AUC (5x T1/2) appropriate assay - right number of subjects (16-32) cross over study design ** get blood samples + measure Cplasma to get AUC and Cmax ratios for each individual, average out

Question 27

Criteria for bio-equivalence

Answer 27

90% CI for AUC and Cmax to be entirely bw 0.8 and 1.25 (must be 90% they in this range) - point estimate for AUC and Cmax should be close to 1 to ensure in range CI must be as narrow as possible (increase n and decrease SD)